PLEASE SELECT THE CATEGORY ON THE LEFT
BNP
Heart failure is an important clinical syndrome which compromises left ventricular systolic or diastolic function or a combination of both. Heart failure occurs when the heart is unable to pump blood at a rate sufficient for metabolic requirements. Its most common causes are coronary artery disease, hypertension, valvular heart diseases and cardiomyopathies. Accurate and early diagnosis is important since effective therapeutic interventions (e.g., angiotensin converting enzyme inhibitors, beta-blockers) are available, which improve both morbidity and mortality. Based on clinical signs and symptoms, the severity of heart failure is classified into four classes of increasing disease progression according to the New York Heart Association classification (NYHA class I – IV). The natriuretic peptide system is a family of structurally similar but genetically distinct peptides, which include atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) of myocardial cell origin and C-type natriuretic peptide (CNP) of endothelial cell origin. These peptides are characterized by a common 17 amino acid ring structure with a disulfide bond between two cysteine residues.
The cardiac natriuretic peptides are the naturally occurring antagonists of the renin-angiotensin-aldosterone system and of the sympathetic nervous system. They promote natriuresis and diuresis, act as vasodilators, and exert antimitogenic effects on cardiovascular tissues. ANP and BNP are secreted by the heart in response to hemodynamic stress. Increased levels of BNP are produced mainly in response to left ventricular wall stretch and volume overload. ANP and BNP are expressed dominantly in the atria and ventricles,respectively, and are important in regulation of blood pressure, electrolyte and volume homeostasis.
CKMB MASS
The quantitation of CK-MB levels in serum is used as an aid in the diagnosis of myocardial injury. Elevated CK-MB levels are associated with myocardial cell death and damage due to acute myocardial infarction (AMI). CK-MB levels can be detected as a result of myocardial injury within 3 to 8 hours following the onset of chest pain with peak concentrations being achieved within 12 to 24 hours and usually returning to baseline levels within 24 to 48 hours. CK-MB samples analyzed at the appropriate time intervals can detect this typical rise and fall pattern, which is indicative of myocardial cell damage. Some myocardial infarctions are relatively minor and produce very low quantities of CK-MB. Therefore, it is important to have a sensitive assay that can detect these minor increases in CK-MB levels.
CKMB ISOENZYME
The Dimension MBI method is a modification of the International Federation of Clinical Chemistry (IFCC) creatine kinase (CK) primary reference 37 °C procedure, adapted for use on the Dimension® clinical chemistry system.
The MB isoenzyme of creatine kinase is used as a marker of cardiac muscle cell damage, and may be especially useful to detect re-infarction after a prior event. Normally an intracellular enzyme, CK-MB begins to appear in blood about 4 to 6 hours after the onset of myocardial damage, peaking at about 24 hoursafter a single event. CK-MB activity declines and returns to normal within about three days.
Calculation of the relative percentage of CK-MB isoenzyme activity in the total CK activity can aid in distinguishing acute coronary syndromes from non-cardiac events.
D-DIMER
Assays for D-dimer can be performed directly in plasma by virtue of monoclonal antibodies which are able to identify fibrin-specific epitopes without cross-reactivity with fibrinogen or its degradation products. D-dimer reflects the presence of stabilized fibrin and this has made this marker a useful tool in the diagnosis of venous thromboembolism (VTE). Quantitative D-dimer assays based on ELISA techniques have a high sensitivity for the presence of an occluding thrombus and,consequently, are particularly useful in excluding venous thromboembolic disease.
In conjunction with assessment of clinical pretest probability, it is possible to safely rule out the diagnosis of deep vein thrombosis (DVT) and pulmonary embolism(PE) in suspected outpatients when the concentration of D-dimer is below a predefined cut-off (determined by rigorous clinical studies). The clinical utility of D-dimer ELISA assays in the diagnostic work-up of suspected DVT or PE resides in the significant reduction in the number of imaging tests that are required with a concomitant reduction in the total cost of diagnosis. D-dimer is not specific for DVT/PE and elevated levels are also observed in a variety of other conditions where activation of coagulation and fibrinolysis occurs (e.g.surgery, trauma, infection, inflammation, pregnancy, cancer). This makes D-dimer less useful for exclusion of DVT or PE in hospitalized patients due to the high proportion of comorbid conditions associated with elevated D-dimer levels. Under certain conditions, lower than expected D-dimer results may occur giving rise to false-negatives. Therefore, it is not safe to use D-dimer for exclusion of VT/PE in patients with high pre-test probability, long duration of DVT/PE symptoms (more than one week) or already under anticoagulant treatment
HIGH SENSITIVITY CRP
C-Reactive Protein is one of the “acute phase” proteins, the serum or plasma levels of which rise during a general, unspecific response to infections and non-infectious inflammatory processes such as rheumatoid arthritis, cardiovascular disease and peripheral vascular disease. CRP is synthesized in the liver and is normally present as a trace constituent of serum or plasma. In various disease states resulting in tissue injury, infection or inflammation, CRP values may rise above normal after an acute event. Since elevated CRP values are always associated with pathological changes, the CRP assay provides useful information for the diagnosis, therapy and monitoring of inflammatory processes and associated diseases. Increases in CRP values are non-specific and should not be interpreted without a complete clinical history. When using CRP to assess risk of cardiovascular and peripheral vascular disease, measurements should be compared to previous values. Measurement of CRP by high sensitivity assays may add to the predictive value of other markers used to assess the risk of cardiovascular and peripheral vascular disease.
HIGH SENSITIVITY TROPONIN I
The troponin complex, consisting of subunits I, T and C, is bound to the myofibrillar thin filaments of striated muscle where it plays a role in the calcium-mediated regulation of muscle contraction. Distinct isoforms of troponin I and T exist in cardiac myocytes and can be specifically measured by immunoassays when released in blood. Because of its high myocardial tissue specificity, cardiac troponin (I or T) is the preferred marker for the detection of myocardial injury, and has become the standard as an aid in the diagnosis of myocardial infarction (MI) in the clinical setting of cardiac ischemia. Cardiac troponin I (cTnI) levels rise rapidly after the onset of myocardial injury and fall to normal levels within 7 days. In view of this rising and falling pattern, serial measurements of cTnI are recommended with blood samples drawn at presentation and after 6-9 hours; occasionally a third sample may be required after 12-24 hours. With high-sensitivity cTnI assays, the second sample is recommended to be drawn after 3 hours.
MYOGLOBIN
Myoglobin is a 17,800 Dalton intracellular, oxygen-binding, heme protein, found in cardiac and skeletal muscle. Myoglobin is noted for its rapid release into the circulation following tissue injury. Elevated levels of myoglobin can be found in conditions of muscle damage, such as acute and chronic skeletal muscle disease, renal failure, myocarditis, open-heart surgery, and after heavy exercise.
Due to increased public awareness, patients present early to the emergency department after onset of symptoms of myocardial infarction. Administering thrombolytic therapy within the first 6 hours of onset of chest pain is important to the prognosis of these patients and essential for early reperfusion with a positive clinical outcome. Myoglobin releases into the circulation as early as 2 to 4 hours after cell damage, peaks at between 9 and 12 hours, and returns to normal within 24 to 36 hours. In the absence of skeletal muscle trauma, myoglobin has been used as an early indicator of myocardial infarction, and therefore as a rule out indicator.
Myoglobin has a negative predictive value of 99%, which improves the rule out capabilities of the emergency department and helps reduce the number of patients inappropriately admitted to the Coronary Care Units with symptoms atypical of acute myocardial infarction. When used incombination with other cardiac markers such as CK-MB or troponin I, myoglobin is a valuable diagnostic tool to be used in the early evaluation of the potential acute myocardial infarction patient.
NT-proBNP
B-type natriuretic peptide (BNP) is a hormone produced by your heart. N-terminal (NT)-pro hormone BNP (NT-proBNP) is a non-active prohormone that is released from the same molecule that produces BNP. Both BNP and NT-proBNP are released in response to changes in pressure inside the heart. These changes can be related to heart failure and other cardiac problems. Levels goes up when heart failure develops or gets worse, and levels goes down when heart failure is stable. In most cases, BNP and NT-proBNP levels are higher in patients with heart failure than people who have normal heart function.
TnI-ULTRA
The high-sensitivity cardiac troponin test can detect very small levels of troponin T in the bloodstream. The normal range (value) for high-sensitivity cardiac troponin T test (hs-cTnT) is 14 ng/l. This cutoff for the “normal” level of troponin T was determined by looking at several studies of patients who were “apparently healthy” (no heart complaints) and had this level of troponin T in the bloodstream as a baseline. Thus, when the high-sensitivity cardiac troponin T test detects levels above 14 ng/l, heart damage or heart attack is likely. As the high-sensitivity cardiac troponin T test becomes more widely used, further refinement in the cutoff levels for normal troponin T is expected based on patient’s age, sex, underlying medical conditions, and ethnicity.
TROPONIN I
A troponin test measures the level of troponin in your blood. Troponin is a type of protein found in the muscles of your heart. Troponin isn't normally found in the blood. When heart muscles become damaged, troponin is sent into the bloodstream. As heart damage increases, greater amounts of troponin are released in the blood.
High levels of troponin in the blood may mean you are having or recently had a heart attack. A heart attack happens when blood flow to the heart gets blocked. This blockage can be deadly. But quick diagnosis and treatment can save your life.
The test is most often used to diagnose a heart attack. It is sometimes used to monitor angina, a condition that limits blood flow to the heart and causes chest pain. Angina sometimes leads to a heart attack.
GALECTIN-3
Galectin-3 is a member of the galectin family, which are β-galactoside-binding lectins with ≥1 evolutionary conserved carbohydrate-recognition domain. It binds proteins in a carbohydrate-dependent and -independent manner. Galectin-3 is predominantly located in the cytoplasm; however, it shuttles into the nucleus and is secreted onto the cell surface and into biological fluids including serum and urine. It serves important functions in numerous biological activities including cell growth, apoptosis, pre-mRNA splicing, differentiation, transformation, angiogenesis, inflammation, fibrosis and host defense. Numerous previous studies have indicated that galectin-3 may be used as a diagnostic or prognostic biomarker for certain types of heart disease, kidney disease and cancer. With emerging evidence to support the function and application of galectin-3, the current review aims to summarize the latest literature regarding the biomarker characteristics and potential therapeutic application of galectin-3 in associated diseases.
DIGOXIN
Digoxin belongs to the class of compounds known as digitalis glycosides, and is the most commonly prescribed drug for congestive heart failure (CHF). Digoxin strengthens the contraction of the cardiac muscle and reduces heart rate by improving cardiac output. In addition, digoxin therapy is also indicated in most cases of atrial fibrillation and atrial flutter whether or not CHF is present. Therapeutically, digoxin is effective within a narrow serum concentration range. Knowledge of the serum level is important for establishing optimal doses for the patient and for diagnosingdigoxin toxicity. Toxic levels can be reached from repeated doses when renal function is impaired because 60 to 90% of digoxin is excreted in the urine unchanged. Other complications that add to digoxin toxicity include:
• variation in gastrointestinal absorption
• variation in nonrenal excretion
• an inaccurate history of dosage
Digoxin toxicity is a frequent complication of digoxin therapy. In patients with CHF, symptoms of digoxin toxicity frequently resemble symptoms of CHF itself. In other words, high toxic levels of digoxin often mimic sub-therapeutic levels, thereby complicating therapy. Some patients require or tolerate doses that are highly toxic for other patients. Patients exhibiting toxic effects are frequently elderly individuals and those with impaired renal function. Therefore, each serum level must be interpreted with the patient’s clinical status in mind.
ANTI-Tg
Thyroglobulin (Tg) is a large, heterogeneous glycoprotein (MW 660,000) found in the follicular cells of the thyroid. Thyroglobulin plays an important role in the biosynthesis of thyroid hormones, T3 and T4. In the thyroid follicular cells, thyroid peroxidase catalyzes the iodination of tyrosyl groups within thyroglobulin. Iodinated thyroglobulin is stored in the colloid of the follicle and serves as a storage reservoir for T3 and T4. When the thyroid gland is stimulated, thyroglobulin is degraded and the thyroid hormones, T3 and T4, are released into the bloodstream. The measurement of autoantibodies against thyroglobulin is useful in identifying patients with autoimmune thyroid disease. Levels of anti-Tg antibodies are increased in 80 to 100% of patients with Hashimoto’s or chronic thyroiditis, 60 to 70% of patients with Graves’ disease, and in 10 to 20% of patients with subacute thyroiditis. Because of the heterogeneity of thyroglobulin, anti-thyroglobulin antibodies have been detected in other disease states, in elderly patients and also in clinically normal, euthyroid patients. Anti-Tg antibodies have been detected in patients with idiopathic Addison’s disease and in some patients with Type I diabetes mellitus.
ANTI - TPO
Thyroid peroxidase (TPO) is a membrane bound glycosylated heme-containing protein found in the apical membrane of the thyroid follicular cells. TPO, the major component of a large protein known as thyroid microsomal antigen, catalyzes the iodination of the tyrosyl groups in thyroglobulin esulting in the synthesis of thyroid hormones, T3 and T4.1 Autoimmume thyroid disease is characterized by the presence of autoantibodies against TPO.
The measurement of autoantibodies against thyroid peroxidase is useful in identifying patients with autoimmune thyroid disease. Levels of anti-TPO antibodies are increased in greater than 90% of patients with active autoimmune thyroiditis. Anti-TPO antibodies activate complement and are thought to be significantly involved in thyroid dysfunction and the pathogenesis of hypothyroidism. In patients with autoimmune thyroid disease, anti-TPO antibodies are present in nearly all patients with Hashimoto’s thyroiditis and in greater than 70% of patients with Graves’ disease.
Anti-TPO antibodies are also present in patients with atropic thyroiditis and primary myxedema. Low levels of anti-TPO antibodies can be detected in healthy individuals with normal thyroid function. The clinical significance of this has not been determined. Levels of anti-TPO antibodies are increased in women with postpartum thyroiditis. This condition occurs in 5 to 9% of postpartum women. The diagnosis of postpartum thyroiditis is based on the observation of abnormal thyroid function in a postpartum female with a positive anti-TPO antibody level. Although postpartum thyroiditis is associated with anti-TPO antibodies, 50% of anti-TPO positive women do not develop thyroid dysfunction. The measurement of anti-TPO antibodies can be useful in diagnosing maternal Graves’ disease or Hashimoto’s thyroiditis.
FREE T3
Triiodothyronine (3,5,3'-L-triiodothyronine, T3) is a hormone synthesized and secreted from the thyroid gland, and formed by peripheral deiodination of thyroxine (T4). T3 and T4 are secreted into the circulation in response to thyroid stimulating hormone (TSH) and play an important role in regulating metabolism. The T3 and T4 secretion are regulated by a negative feedback mechanism involving the thyroid gland, pituitary gland, and hypothalamus. In the circulation, 99.7% of T3 is reversibly bound to transport proteins, primarily thyroxine_x0002_binding globulin (TBG) and to a lesser extent albumin and prealbumin.1 The remaining T3 does not bind to transport proteins, but is free in the circulation. This unbound fraction of the total T3 concentration is free triiodothyronine (free T3, FT3). Unbound T3 is metabolically active. Free T3 levels correlate with T3 secretion and metabolism. In hypothyroidism and hyperthyroidism, free T3 levels parallel changes in total T3 levels.2 However, measuring free T3 is useful when altered levels of total T3 occur due to changes in T3 binding proteins, especially TBG. TBG levels remain relatively constant in healthy individuals, but certain conditions such as normal pregnancy and steroid therapy can alter these levels. In these conditions, free T3 levels are unchanged, while total T3 levels parallel the changes in TBG.
FREE T4
Thyroxine (3,5,3',5'-tetraiodothyronine, L-thyroxine or T4) is a hormone synthesized and secreted by the thyroid gland and plays an important role in regulating metabolism. Secretion into the circulation is in response to the pituitary hormone TSH (thyroid stimulating hormone) and is regulated by a negative feedback mechanism involving the thyroid gland, pituitary gland, and hypothalamus.
In the circulation, 99.95% of T4 is reversibly bound to transport proteins, primarily thyroxine_x0002_binding globulin (TBG) and to a lesser extent albumin and thyroxine-binding prealbumin (TBPA). The remaining T4 is not bound to transport proteins, but is free in the circulation. This unbound fraction, or free T4 (FT4), is both metabolically active and a precursor to triiodothyronine Free T4 levels correlate with T4 secretion and metabolism. In hypothyroidism and hyperthyroidism, FT4 levels parallel changes in total T4 levels.4 Measuring free T4 is useful when altered levels of total T4 occur due to changes in T4 binding proteins, especially TBG. TBG levels remain relatively constant in healthy individuals, but certain conditions, such as normal pregnancy and steroid therapy, can alter these levels. In these conditions, free T4 levels are unchanged, while total T4 levels parallel the changes in TBG.
T UPTAKE
The thyroid hormones triiodothyronine (T3) and thyroxine (T4) are bound primarily to thyroxine-binding globulin (TBG) and to a lesser extent thyroxine-binding prealbumin (TBPA) and albumin. The ADVIA Centaur CP TUp assay measures the number of unoccupied binding sites on these proteins and is an indirect indicator of thyroid status. T Uptake (TU) and total T4 are used to estimate the amount of circulating free T4. The estimate, or the Free Thyroxine Index (FTI), is a normalized measurement that remains relatively constant in healthy individuals and compensates for abnormal levels of binding proteins, which can occur in many different physical conditions.1-3 Drugs or physical conditions that alter the patient’s TBG levels or drugs that compete with endogenous T4 and T3 for protein-binding sites alter T Uptake results. When serum contains high levels of T3 or T4, as in hyperthyroidism, fewer unoccupied binding sites are available. Conversely, in hypothyroidism, more binding sites are available.
Drugs or physical conditions that alter the patient’s TBG levels or drugs that compete with endogenous T4 and T3 for protein-binding sites alter T Uptake results. When serum contains high levels of T3 or T4, as in hyperthyroidism, fewer unoccupied binding sites are available. Conversely, in hypothyroidism, more binding sites are available.
TBG
Thyroxine-binding globulin (TBG) is one of three major transport proteins, which are primarily responsible for binding to and transporting thyroid hormones to the necessary tissues. The other two serum transport proteins include transthyretin and human serum albumin. While there are higher amounts of albumin in serum, TBG has a greater affinity to thyroxine (T4).[1] Abnormalities in the functionality and amount of TBG can cause variations in the total amount of T4 in the serum, but not in the amount of bioactive free T4. Since the amount of free T4 circulating in the serum remains the same, deficiency in thyroxine-binding globulin often does not lead to adverse metabolic effects seen in an individual with abnormal thyroid hormone levels.[2] However, it can cause errors in the interpretation of thyroid hormone labs, which can ultimately lead to inappropriate treatment. This article illustrates the etiology, diagnosis, and management of thyroxine-binding globulin deficiency.
THYROGLOBULIN
Thyroglobulin (Tg) is a large, heterogeneous glycoprotein (MW 660,000) found in the follicular cells of the thyroid. Thyroglobulin plays an important role in the biosynthesis of thyroid hormones, T3 and T4. In the thyroid follicular cells, thyroid peroxidase catalyzes the iodination of tyrosyl groups within thyroglobulin. Iodinated thyroglobulin is stored in the colloid of the follicle and serves as a storage reservoir for T3 and T4. When the thyroid gland is stimulated, thyroglobulin is degraded and the thyroid hormones, T3 and T4, are released into the bloodstream.
The measurement of autoantibodies against thyroglobulin is useful in identifying patients with autoimmune thyroid disease. Levels of anti-Tg antibodies are increased in 80 to 100% of patients with Hashimoto’s or chronic thyroiditis, 60 to 70% of patients with Graves’ disease, and in 10 to 20% of Patients with subacute thyroiditis. Because of the heterogeneity of thyroglobulin, anti-thyroglobulin antibodies have been detected in other disease states, in elderly patients and also in clinically normal, euthyroid patients. Anti-Tg antibodies have been detected in patients with idiopathic Addison’s disease and in some patients with Type I diabetes mellitus.
TOTAL T3
Triiodothyronine (3,5,3'-L-triiodothyronine, T3) is a hormone that originates from direct thyroid synthesis and secretion (approximately 20%) and from peripheral conversion of T4 to T3 approximately 80%).1 T3 is secreted into the circulation in response to the pituitary hormone TSH (thyroid stimulating hormone). The secretion of T3 is regulated by a negative feedback mechanism involving the thyroid gland, pituitary gland, and hypothalamus.
Although serum levels of T3 are small, it has a greater physiological potency than T4. In the circulation, 99.7% of T3 is reversibly bound to transport proteins, primarily thyroxine binding globulin (TBG) and to a lesser extent albumin and thyroxine binding prealbumin (TBPA). Unbound or free T3 is metabolically active and bound T3 is metabolically inactive, acting as a reserve for free T3.
TBG concentrations remain relatively constant in healthy individuals. However, pregnancy, excess estrogens, androgens, anabolic steroids, and glucocorticoids are known to alter TBG levels and may cause false thyroid values for thyroid function tests. T3 levels in these situations may not accurately reflect thyroid status.
Primary malfunction of the thyroid gland may result in excessive (hyper) or below normal (hypo) release of T3 or T4. In addition, as thyroid function is directly affected by TSH, malfunction of the pituitary or the hypothalamus influences the thyroid gland activity. Disease in any portion of the thyroid-pituitary-hypothalamus system may influence the levels of T3 and T4 in the blood. Diagnostically, T3 concentration is more sensitive to certain thyroid conditions than T4. While T4 levels are a sensitive (and superior) indicator of hypothyroidism, T3 blood levels better define hyperthyroidism. Because T3 concentration in serum changes faster and more markedly than T4, the T3 level is also an excellent indicator of the ability of the thyroid to respond to both stimulatory and suppressive tests. Under conditions of strong thyroid stimulation, the T3 level offers a good estimation of thyroidal reserve as well.
TOTAL T4
Thyroxine (3,5,3',5'-L-tetraiodothyronine, T4) is a hormone synthesized and secreted by the thyroid gland, and plays an important role in regulating metabolism. T4 is secreted into the circulation in response to the pituitary hormone TSH (thyroid stimulating hormone). The secretion of T4 is regulated by a negative feedback mechanism involving the thyroid gland, hypothalamus, and pituitary gland.
In the circulation 99.95% of T4 is reversibly bound to transport proteins, primarily thyroxine binding globulin (TBG) and to a lesser extent albumin and prealbumin. Unbound or free T4 is metabolically active and bound T4 is metabolically inactive, acting as a reserve.
TBG concentrations remain reasonably constant in healthy individuals. However, pregnancy, excess estrogens, androgens, anabolic steroids, and glucocorticoids are known to alter TBG levels and may cause false thyroid values for thyroid function tests. Altered T4 levels in these situations may not accurately reflect thyroid status.
Primary malfunction of the thyroid gland may result in excessive (hyper) or below normal (hypo) release of T4 or T3. In addition, as thyroid function is directly affected by TSH, malfunction of the pituitary or the hypothalamus influences the thyroid gland activity. Disease in any portion of the thyroid-pituitary-hypothalamus system may influence the levels of T4 and T3 in the blood.
TSH 3rd GENERATION
Thyroid-stimulating hormone is a glycoprotein with two non-covalently bound subunits. The alpha subunit is similar to those of follicle-stimulating hormone (FSH), human chorionic gonadotropin (hCG), and luteinizing hormone (LH). The beta subunit of TSH is unique, which results in the specific biochemical and immunological properties of this hormone. TSH is synthesized and secreted by the anterior pituitary in response to a negative feedback mechanism involving concentrations of FT3 (free T3) and FT4 (free T4). Additionally, the hypothalamic tripeptide, thyrotropin-releasing hormone (TRH), directly stimulates TSH production. TSH interacts with specific cell receptors on the thyroid cell surface and exerts two main actions. The first action is to stimulate cell reproduction and hypertrophy. Secondly, TSH stimulates the thyroid gland to synthesize and secrete T3 and T4.
The ability to quantitate circulating levels of TSH is important in evaluating thyroid function. It is specially useful in the differential diagnosis of primary (thyroid) from secondary (pituitary) and tertiary (hypothalamus) hypothyroidism. In primary hypothyroidism, TSH levels are significantly elevated, while in secondary and tertiary hypothyroidism, TSH levels are low.
TRH stimulation differentiates secondary and tertiary hypothyroidism by observing the change in patient TSH levels. Typically, the TSH response to TRH stimulation is absent in cases of secondary hypothyroidism, and normal to exaggerated in tertiary hypothyroidism.
Historically, TRH stimulation has been used to confirm primary hyperthyroidism, indicated by elevated T3 and T4 levels and low or undetectable TSH levels. TSH assays with increased sensitivity and specificity provide a primary diagnostic tool to differentiate hyperthyroid from euthyroid patients.
TSH3 -ULTRA
Third-generation thyroid-stimulating hormone (TSH) assays are generally the most sensitive screening tool for primary hypothyroidism. [1] If TSH levels are above the reference range, the next step is to measure free thyroxine (T4) or the free thyroxine index (FTI), which serves as a surrogate of the free hormone level. Routine measurement of triiodothyronine (T3) is not recommended.
Biotin, a popular health supplement, may interfere with immunoassays of many hormones, resulting in values that are falsely elevated or suppressed, including for thyroid levels. To avoid misleading test results, the American Thyroid Association recommends cessation of biotin consumption at least 2 days prior to thyroid testing. [2]
Results in patients with hypothyroidism are as follows:
Elevated TSH with decreased T4 or FTI
Elevated TSH (usually 4.5-10.0 mIU/L) with normal free T4 or FTI is considered mild, or subclinical, hypothyroidism [3]
TSI
Autoimmune thyroid disease is characterized by the presence of autoantibodies against various thyroid components, namely the thyrotropin receptor (thyroid-stimulating hormone receptor: TSHR), thyroid-peroxidase (TPO), and thyroglobulin (Tg), as well as an inflammatory cellular infiltrate of variable severity within the gland. Among the autoantibodies found in autoimmune thyroid disease, TSHR autoantibodies are most closely associated with disease pathogenesis. All forms of autoimmune thyrotoxicosis (Graves disease, Hashitoxicosis, neonatal thyrotoxicosis) are caused by the production of TSHR-stimulating autoantibodies. The role of the TPO and Tg autoantibodies in either autoimmune thyrotoxicosis or autoimmune hypothyroidism is less well established; they may merely represent epiphenomena. Detectable concentrations of anti-TPO antibodies are observed in most patients with autoimmune thyroid disease (eg, Hashimoto thyroiditis, idiopathic myxedema, and Graves disease).
Autoantibodies that bind and transactivate the TSHR lead to stimulation of the thyroid gland independent of the normal feedback-regulated thyroid-stimulating hormone (TSH) stimulation. These TSHR autoantibodies also are known as long-acting-thyroid-stimulator or thyroid-stimulating immunoglobulins (TSI). Some patients with Graves disease also have TSHR-blocking antibodies, which do not transactivate the TSHR. The balance between TSI and TSHR-blocking antibodies, as well as their individual titers, are felt to be determinants of Graves disease severity. At least 20% of patients with autoimmune hypothyroidism also have evidence either of TSHR-blocking antibodies or, less commonly, TSI.
TSHR autoantibodies may be found before autoimmune thyrotoxicosis becomes biochemically or clinically manifest. Since none of the treatments for Graves disease are aimed at the underlying disease process, but rather ablate thyroid tissue or block thyroid hormone synthesis, TSI may persist after apparent cure.
TSI are IgG antibodies and can, therefore, cross the placental barrier, causing neonatal thyrotoxicosis.
First-order tests for autoimmune thyroid disease include TPO / Thyroperoxidase (TPO) Antibodies, Serum (most suited for suspected cases of autoimmune hypothyroidism) and THYRO / Thyrotropin Receptor Antibody, Serum. Thyrotropin receptor antibody (TSHR-antibody) is a binding assay that detects both TSI and TSHR-blocking autoantibodies; it can be used instead of this TSI assay for most applications, as long as the results are interpreted in the clinical context. The TSHR-antibody test has a shorter turnaround time than the TSI assay, is less expensive, and if interpreted within the clinical context, has excellent correlation with the TSI assay. Specific detection of TSI is accomplished by this second-order bioassay.
Anti B Pertussis Toxin
Bordetella pertussis, which causes whooping cough, is a small, Gram-negative bacterium in the coccobacillus family. It is transmitted by airborne droplets and is highly contagious.
Whooping cough is one of the most dangerous infectious diseases for infants; it is potentially fatal. In adolescents and adults the infection usually has milder symptoms and is often not recognized as whooping cough. This may cause individuals to transmit the disease to vulnerable younger children.
Laboratory diagnosis in infants can be accomplished through direct detection after bacterial culture of by PCR. In adolescents and adults -- who usually only consult a doctor if symptoms persist for a long time -- indirect serological methods are more suitable. These include ELISA tests to detect the pertussis toxin produced by these bacteria, which is the most important pathogenic factor.
The Anti-B. pertussis Toxin ELISA tests from ORGENTEC Diagnostika (ORG 916A, ORG 916G) use highly purified, native pertussis toxin as antigen for the detection of IgA or IgG antibodies. These pure pertussis toxin ELISA tests allow for the quantification of the antibodies. Both ORGENTEC assays are calibrated against international WHO standards.
According to recommendations of the European Consensus for Reference Laboratories for Bordetella pertussis, quantitative results like those obtained with the ORGENTEC Anti-B. pertussis Toxin IgA and IgG tests can confirm recent exposure to this pathogen. The guidelines propose a two-step cut-off, which is applicable if the patient has not been vaccinated within the last 12 months.
Anti-Borrelia
The ORGENTEC Anti-Borrelia kits use different sets of recombinant proteins displaying highly specific immunodominant epitopes of the major human pathogenic Borrelia species. This makes it possible to detect antibodies against the primary causes of Lyme disease in Asia, Europe, and the USA.
The tailor-made antigen profiles cover all of the epitopes necessary for specific antibody recognition, avoiding cross-reactivity with other pathogens or commensal bacteria.
The determination of IgG and IgM antibodies plays an important role in chronic infections, especially Lyme arthritis and neuroborreliosis. In cases of Lyme arthritis, serum samples usually have very high IgG titres in the absence of IgM antibodies. The detection of intrathecal antibody production is proof of chronic neuroborreliosis.
Anti-Chlamydia pneumoniae
The Alegria® test systems for the detection of different immunoglobulin subtypes of antibodies are useful for the differentiation of acute (IgM), previous (IgG), or chronic infections (IgA) with this bacterial pathogen and for the determination of the patient’s immune status. All ORGENTEC Anti-Chlamydia pneumoniae tests use elementary and reticulate bodies of Chlamydia pneumoniae as antigens. A special preparatory technique has significantly increased the species specificity of this test toward other human pathogenic species of Chlamydia such as Chlamydia trachomatis and Chlamydia psittaci.
Anti-Chlamydia trachomatis
Infections with C. trachomatis are often asymptomatic and gradually proceeding, therefore primary infections are often underdiagnosed and infected individuals are not treated in sufficient time. After primary infection, IgM, IgA, and IgG antibodies can be detected successively in serum samples. IgG antibodies are generally considered as markers for any contact with the pathogen irrespective of disease stage. IgM antibodies are characteristic for acute infection, and IgA antibodies indicate ongoing progression of a chronic infection. All ORGENTEC Anti-chlamydia trachomatis tests use recombinant, type-specific antigens of the serotype-encompassing major outer membrane protein complex (MOMP) of Chlamydia trachomatis. These are joined by two complementary recombinant antigens, TARP and CPAF, which also react with antigens specific to Chlamydia trachomatis. This increases the sensitivity and specificity of this test relative to conventional ELISAs that are based only on MOMP
Anti-EBV (EBNA-1) IgG
Anti-EBV (EBNA-1) IgG is an ELISA-based, automated, in-vitro test system for the quantitative determination of IgG antibodies against Epstein-Barr virus nuclear antigen 1 (EBNA-1) in human serum or plasma.
Epstein-Barr virus (EBV) is the cause of infectious mononucleosis (glandular fever, kissing disease). The pathogen first infects the salivary glands, which leads to general flu-like symptoms. About six to eight weeks after onset of symptoms, patients form IgG antibodies against EBNA-1. The presence of these antibodies indicates transition from the active to the latent phase of the disease. Therefore, detection of IgG antibodies against EBNA-1 allows for exclusion of primary EBV infection Acute EBV infections lead to the unspecific stimulation of the immune system, which can effect false positive results in tests for other antibodies. For differential diagnosis when symptoms are unclear, it is thus always necessary to determine the patient’s EBV status.
Anti-EBV (VCA) IgM
Anti-EBV (VCA) IgG is an ELISA-based, automated, in-vitro test system for the quantitative determination of IgG antibodies against Epstein-Barr virus viral capsid antigen (VCA) in human serum or plasma.
Anti-EBV (VCA) IgG
Epstein-Barr virus (EBV) is the cause of infectious mononucleosis (glandular fever, kissing disease). In the early stage of the disease, IgM and IgG antibodies against VCA are successively detectable. About three weeks after the onset of symptoms, the maximum concentration of IgM antibodies against the VCA peptide is attained; the highest concentration of VCA IgG antibodies is reached after about six weeks. This high concentration of VCA IgG antibodies remains throughout the life of the patient.
Anti-EBV (ZEBRA) IgM
Anti-EBV (ZEBRA) IgM is an ELISA-based, automated, in-vitro test system for the quantitative determination of IgM antibodies against the ZEBRA protein of the Epstein-Barr virus (EBV) in human serum or plasma. It is used to detect an acute primary infection with EBV.
It is generally possible to differentiate between the latent and lytic stages of infection with EBV. In the latent phase, few copies of the viral DNA remain as episomes in the infected cells. These are replicated during cell division and are passed on to the daughter cells. In contrast, during the lytic stage, all viral genes necessary for the formation of complete virus particles are activated. One of the earliest resulting gene products is the ZEBRA protein (BamHI-Z-encoded Epstein-Barr virus replication activator), an immediate early protein (IEA) of EBV. This is a DNA-binding nuclear protein that activates other genes of the lytic phase; its expression precedes the synthesis of other molecules of the lytic phase.
Anti-HAV IgG
Anti-HAV immunoglobulin G (IgG) appears soon after IgM and generally persists for many years. The presence of anti-HAV IgG in the absence of IgM indicates past infection or vaccination rather than acute infection. IgG provides protective immunity.
Anti-HAV IgM
Hepatitis A is caused by infection with the hepatitis A virus. HAV is a 27 nanometer single-stranded, nonenveloped, RNA virus that is classified as a picornavirus. Transmission of hepatitis A is usually via the fecal-oral route and infection occurs mainly due to contaminated food or poor sanitary conditions.
Hepatitis A virus replicates in the liver. The virus is excreted in the bile and shed in the stool. Only one serotype has been observed among HAV isolates collected from various parts of the world. The average incubation period for HAV infection is 30 days with a range of 15 to 40 days. Chronic infection has not been reported to occur following HAV infection. Symptoms last approximately 2 weeks and include hepatomegaly, jaundice, dark urine, fatigue, and gastrointestinal distress such as anorexia, nausea, vomiting, and abdominal pain. At the onset of symptoms resulting from HAV infection, antibody to HAV is detectable. The early antibody response is largely comprised of the IgM antibody subclass. Anti-HAV IgM is detectable usually for 3 to 6 months after the onset of illness, whereas anti-HAV IgG can persist indefinitely. Because of the transient production of anti-HAV IgM, its presence in sera indicates ongoing or recent infection and is the most useful serological marker for diagnosing acute HAV infection.
Since symptomatic hepatitis A viral infections can not be clinically distinguished from hepatitis B or C viral infections, serological testing is important for proper diagnosis.
Anti-HAV Total
Hepatitis A is caused by infection with the hepatitis A virus. HAV is a 27-nanometer single-stranded, nonenveloped, RNA virus that is classified as a picornavirus. Transmission of hepatitis A is via the fecal-oral route and infection occurs mainly due to contaminated food or poor sanitary onditions.
Hepatitis A virus replicates in the liver. The virus is excreted in the bile and shed in the stool. Only one serotype has been observed among HAV isolates collected from various parts of the world. The average incubation period for HAV infection is 30 days with a range of 15 to 40 days. Chronic infection has not been reported to occur following HAV infection. Symptoms last approximately 2 weeks and include hepatomegaly, jaundice, dark urine, fatigue, and gastrointestinal distress such as anorexia, nausea, vomiting, and abdominal pain. At the onset of symptoms resulting from HAV infection, antibody to HAV is detectable. The early antibody response is largely comprised of the IgM antibody subclass. Anti-HAV IgM is detectable for 3 to 6 months after the onset of illness, whereas anti-HAV IgG can persist indefinitely. The specific determination of anti-HAV IgM is the most useful serological marker for diagnosing acute HAV infection. Total anti-HAV is used primarily for determination of previous exposure to Hepatitis A virus.
The ADVIA Centaur CP HAV Total assay detects all classes of antibodies against hepatitis A virus. The detection of anti-HAV total activity is used to identify susceptible individuals and to determine cquisition of immunity after vaccination.
Anti-HBc Total
Hepatitis B core antibodies (anti-HBc Ab) appear shortly after the onset of symptoms of hepatitis B infection and soon after the appearance of hepatitis B surface antigen (HBsAg). Initially, anti-HBc Ab consist almost entirely of the IgM class, followed by appearance of anti-HBc IgG, for which there is no commercial diagnostic assay.
The anti-HBc total antibodies test, which detects both IgM and IgG antibodies, and the test for anti-HBc IgM antibodies may be the only markers of a recent hepatitis B infection detectable in the "window period." The window period begins with the clearance of HBsAg and ends with the appearance of antibodies to hepatitis B surface antigen (anti-HBs Ab). Anti-HBc total Ab may be the only serologic marker remaining years after exposure to hepatitis B.
Anti-HBc IgM
Anti-HBc (IgG and IgM) antibodies are the body’s first response to a hepatitis B virus (HBV) infection. These antibodies are directed against a portion of the HBV called the core. IgM anti-HBc antibodies appear shortly after the symptoms and appearance of HBsAg. They last 4 to 8 months (sometimes up to 2 years) and are then replaced by IgG anti-HBc antibodies. IgM anti-HBc results are interpreted in light of HBsAg and anti-HBs results, among others.
A negative IgM anti-HBc result may indicate that there is no recent or previous HBV infection (negative HBsAg, anti-HBs and IgG anti-HBc) or that the individual is in the acute phase of the disease and has not yet built up a defence (positive HBsAg, negative anti-HBs) or that the virus has been reactivated in a chronic carrier. IgM (and IgG) anti-HBc will also be negative in a successfully vaccinated individual.
A positive IgM anti-HBc result indicates that the body has begun to defend itself against HBV. When combined with a negative HBsAg, the recovery period is underway and the IgG anti-HBc test is expected to quickly become positive. If HBsAg is still positive, the individual is either still in the acute phase of the disease and the combination of positive HBsAg/IgG anti-HBc / negative anti-HBs may indicate an active chronic infection.
Anti-Hbe
Approximately 5% of the world population is infected by the hepatitis B virus (HBV) which causes a necroinflammatory liver disease of variable duration and severity. Chronically infected patients with active liver disease carry a high risk of developing cirrhosis or hepatocellular carcinoma. The immune response to HBVencoded antigens is responsible both for viral clearance and for disease pathogenesis during this infection.
Hepatitis B can be transmitted through sexual contact, exposure to blood products, or perinatally.
Perinatal transmission can be as high as 90% in women who are chronically infected with HBV, in highly endemic areas or in regions with no systematic testing of pregnant women. The child ecomes a chronic carrier of HBs antigen in 90% of cases (1).The C gene of the HBV viral genome can express two distinct proteins: 1) core protein (HBc Ag) which forms the nucleocapsid, 2) e non-particulate protein (HBe Ag).
A positive result for anti-HBe in patients recovering from acute hepatitis indicates normal recovery, particularly if HBsAg and HBe Ag are no longer detectable. In an HBV carrier, a positive anti-HBe result usually indicates inactivity of the virus and low infectivity of the patient (5). However a positive anti-HBe result in the presence of a positive HBV-DNA test result can indicate active viral replication and progression of liver disease in a carrier (5). HBV mutants, unable to secrete HBe Ag, can prevail over wild-type HBVs in patients with severe acute and chronic hepatitis B and in chronic HBs Ag carriers at the time of HBe Ag/anti-HBe seroconversion (6). The VIDAS HBe/anti-HBe assay aids in detecting the presence of HBe antigen or anti-HBe antibody which are respectively, except for infections by mutant HBe viruses, markers for a viral replication phase or an evolution towards normalization.
Anti-HBs
The hepatitis B virus (HBV) is responsible for acute and chronic hepatitis infections, possibly evolving to cirrhosis or primary liver cancer. Chronicity occurs in 5 to 10% of cases in adults, but up to 90% of cases in infants following perinatal transmission. Currently, more than 360 million people worldwide are chronic carriers of the virus (1). The hepatitis B virus can be transmitted by parenteral and perinatal pathways or through sexual contact. People most at risk are health workers, drug addicts, those with multiple sexual partners, multiple transfusion or hemodialysis patients, as well as close friends and family of an infected subject, and newborns of an infected mother (2). HBs antigen (HBsAg) appears several days to several weeks after contact with the virus and can persist for several months: in this case, the infection is considered to be “chronic”. Disappearance of the HBs antigen is normally followed by the appearance of Anti-HBs, which is a sign of recovery. In this case, the presence of Anti-HBs is associated with that of Anti-HBc.
Anti-HCV
The Hepatitis C virus (HCV) discovered in 1989 using advanced molecular biology techniques, was rapidly found to account for the majority of those patients with non-A non-B hepatitis. HCV represents a major worldwide public health problem requiring global action for the diagnosis, treatment and prevention of this infection (1). HCV is primarily parenterally transmitted through direct blood-to-blood contact between two people: use of unsterilized injection devices and transfusion of unscreened blood or blood products (2). The disease frequently progresses to chronic hepatitis C (80%), exposing patients to a greater risk of hepatic complications such as cirrhosis or hepatocellular carcinoma. (3). The current standard of treatment for HCV is a combination of two drugs: pegylated interferon and ribavirin, but due to the high genetic variability of HCV (4), it is still only partially effective: viral eradication in less than 50% of patients infected with genotype 1 hepatitis C virus against approximately 80% of patients infected with genotype 2 or 3. New herapeutic options are under study to offer more effective and safer personalized treatments (5,6).
Diagnosis of patients infected with HCV can be performed using two categories of virological tests: indirect tests, and direct tests (7). Indirect serological tests are third-generation enzyme immunoassays that detect antibodies to HCV. The antigens used in the tests to detect antibodies are from the structural and non_x0002_structural regions of the HCV (8) (capsid, protein, cofactors, polymerase, etc.). The presence of anti-HCV antibodies indicates that an individual may have been infected with HCV in the past or may have an ongoing HCV infection. To confirm the presence of active HCV infection, a positive serological test can be completed using direct tests (e.g.: molecular assays that detect RNA genomes). The results will be used to guide patient management and determine the optimal duration of treatment.
Anti-Helicobacter pylori IgA
Helicobacter pylori is a Gram-negative, helical bacterium that colonizes the human stomach. More virulent type I strains are differentiated from less virulent type II strains. The former have additional pathogenic factors like vacuolating cytotoxin VacA and cytotoxin-associated CagA. About half of the global human population is infected with H. pylori. The infection is often acquired in early childhood and usually remains undetected. However, about 10-20 % of infected individuals develop severe stomach problems ranging from gastric ulcers to lymphoma and adenocarcinoma of the stomach. Left untreated, H. pylori generally remains in the stomach throughout the life of the individual. Eradication is only possible by treatment with a combination of special antibiotics. There are a variety of invasive and non-invasive methods for detecting H. pylori infections. Non-invasive serological analyses are easy to carry out and have high sensitivity and specificity. Antibodies against the bacterial pathogenicity factors, particularly CagA are statistically more prevalent in cases of more serious infection. Specific antibodies against H. pylori are detectable by ELISA shortly after infection. The immune response to H. pylori generally begins with the formation of IgM antibodies, followed by increasing titres of IgG and IgA antibodies, which remain over the course of the infection.
Anti-Helicobacter pylori IgG
Helicobacter pylori is a Gram-negative, helical bacterium that colonizes the human stomach. More virulent type I strains are differentiated from less virulent type II strains. The former have additional pathogenic factors like vacuolating cytotoxin VacA and cytotoxin-associated CagA. About half of the global human population is infected with H. pylori. The infection is often acquired in early childhood and usually remains undetected. However, about 10-20 % of infected individuals develop severe stomach problems ranging from gastric ulcers to lymphoma and adenocarcinoma of the stomach. Left untreated, H. pylori generally remains in the stomach throughout the life of the individual. Eradication is only possible by treatment with a combination of special antibiotics. There are a variety of invasive and non-invasive methods for detecting H. pylori infections. Non-invasive serological analyses are easy to carry out and have high sensitivity and specificity. Antibodies against the bacterial pathogenicity factors, particularly CagA are statistically more prevalent in cases of more serious infection. Specific antibodies against H. pylori are detectable by ELISA shortly after infection. The immune response to H. pylori generally begins with the formation of IgM antibodies, followed by increasing titres of IgG and IgA antibodies, which remain over the course of the infection.
Alegria® Anti-Helicobacter pylori IgG is an ELISA-based, automated, in-vitro test system for the quantitative determination of IgG antibodies against Helicobacter pylori in human serum or plasma.
Anti-Hepatitis E Virus
The hepatitis E virus is a small, non-enveloped virus with a single-stranded RNA genome. Along with hepatitis A, hepatitis E is one of the primary causes of acute hepatitis. The virus is transmitted by a faecal-oral route, through contaminated drinking water countries and through undercooked meat. Laboratory diagnosis of HEV infection depends on the detection of impaired liver function (elevated serum level of liver enzymes), as well as the direct or indirect detection of the virus. Because cases of hepatitis E cannot be distinguished clinically from other types of acute viral hepatitis, hepatitis E should always be considered in the differential diagnosis of acute hepatitis. During the viremic phase, HEV RNA can be detected in both the blood and stool by means of RT-PCR. However, the serological detection of virus-specific antibodies is more meaningful. The IgM response is generally positive four weeks after infection when clinical symptoms begin. The IgG antibodies then increase and reach their maximum about four weeks later. Anti HEV antibodies are predominantly directed against epitopes of ORF2. This test uses recombinant ORF2 from genotypes 1 and 3 as antigen. Due to cross reactions, antibodies against genotypes 2 and 4 are also detected.
Anti-HSV-1
Herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2) are pathogenic to humans and belong to the herpesvirus family. All herpesviruses are composed of relatively large DNA genomes. Like other herpesviruses, HSV-1 and HSV-2 follow a productive lytic infection and establish a latent lifelong infection in the host. In the latent stage, the production of infectious virus particles is inhibited but periodic reactivation and successive cycles of virus replication lead to reproduction and spreading to further susceptible persons.
HSV-1 and HSV-2 infect humans all over the world, but seroprevalence rates vary by geographic region; with highest levels in Africa south of the Sahara and lower levels in western Europe. In general, HSV-1 infection rates are markedly higher compared to HSV-2. Both, HSV-1 and HSV-2 infect epithelial cells of the mucous membranes, HSV-1 localizes preferentially in the orofacial region (Herpes labialis) and HSV-2 in genital and anal areas (Herpes genitalis). The infection only spreads when a susceptible person comes into close contact with tissue or body fluids containing the virus. In the acute stage of infection skin lesions with characteristic blisters (“cold sore”) occur. Severe manifestations, such as an HSV-associated encephalitis or herpes corneae are rare. Herpes simplex virus infects the neurones of the dorsal root ganglia, where it causes lifelong latent infection. The virus is often reactivated, leading to recurrent symptoms.
In general, primary HSV-1 infection occurs during childhood, while HSV-2 infection is usually acquired sexually in early adulthood. Perinatal infection of the newborn can lead to a severe generalized neonatal herpes infection (Herpes neonatorum). Thus it is always recommended to determine a woman’s HSV status during pregnancy, including discrimination of HSV-1 und HSV-2, to estimate the newborn’s risk for perinatal infection.
In the early phase of primary infection the corresponding IgG antibodies are not yet produced. As a rule, IgG antibodies against HSV-1 are formed two to three months after a primary infection with the type 1 herpes simplex virus. IgG-class antibodies against glycoprotein G2 are detectable several weeks after primary infection. This test uses HSV-1 glycoprotein G as coating antigen.
Anti-HSV-1/2
The human pathogenic type 1 and 2 herpes simplex viruses (HSV-1 and HSV-2) infect epithelial cells of the mucous membranes: HSV-1 primarily in the head area (herpes labialis), HSV-2 in the genital and anal areas (herpes genitalis). In the acute stage, the infection causes formation of characteristic blisters. In transitioning to the latent stage, these viruses enter the sensory nerves and spinal ganglia, where they persist throughout the lifetime of the patient. They are often reactivated, causing a recurrence of symptoms. It is always recommended to determine a woman’s HSV status during pregnancy to estimate the newborn’s risk for perinatal infection. Detection of IgM antibodies against HSV virus is important to confirm an acute primary infection, which has been detected via PCR. Besides, IgM antibodies may also be detectable in cases of recurrent or persistent infection. IgG antibodies against the type-specific glycoprotein G1 are formed two to three months after a primary infection with the type 1 herpes simplex virus. IgG-class antibodies against glycoprotein G2 are detectable several weeks after primary infection.
Anti-HSV-2
Herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2) are pathogenic to humans and belong to the herpesvirus family. All herpesviruses are composed of relatively large DNA genomes. Like other herpesviruses, HSV-1 and HSV-2 follow a productive lytic infection and establish a latent lifelong infection in the host. In the latent stage, the production of infectious virus particles is inhibited but periodic reactivation and successive cycles of virus replication lead to reproduction and spreading to further susceptible persons. HSV-1 and HSV-2 infect humans all over the world, but seroprevalence rates vary by geographic region; with highest levels in Africa south of the Sahara and lower levels in western Europe.
In general, HSV-1 infection rates are markedly higher compared to HSV-2. Both, HSV-1 and HSV-2 infect epithelial cells of the mucous membranes, HSV-1 localizes preferentially in the orofacial region (Herpes labialis) and HSV-2 in genital and anal areas (Herpes genitalis). The infection only spreads when a susceptible person comes into close contact with tissue or body fluids containing the virus. In the acute stage of infection skin lesions with characteristic blisters (“cold sore”) occur. Severe manifestations, such as an HSV-associated encephalitis or herpes corneae are rare. Herpes simplex virus infects the neurones of the dorsal root ganglia, where it causes lifelong latent infection. The virus is often reactivated, leading to recurrent symptoms.
In general, primary HSV-1 infection occurs during childhood, while HSV-2 infection is usually acquired sexually in early adulthood. Perinatal infection of the newborn can lead to a severe generalized neonatal herpes infection (Herpes neonatorum). Thus it is always recommended to determine a woman’s HSV status during pregnancy, including discrimination of HSV-1 und HSV-2, to estimate the newborn’s risk for perinatal infection. In the acute stage of infection direct detection of the virus from the vesicles content via PCR is indicated.
In addition, detection of IgM antibodies against HSV is important to confirm acute primary infection. However, not all patients produce IgM antibodies in the acute phase of infection; besides, IgM antibodies may also be detectable in cases of recurrent or persistent infection Since HSV-1 and HSV-2 are immunologically very similar, almost all antibodies formed in an infected individual are cross-reactive. The HSV type-specific glycoprotein G is an exception, because these antigens of both viruses differ sufficiently. However, glycoprotein G almost only induces the formation of IgG antibodies. Therefore, detection of IgG antibodies against HSV-1 glycoprotein G (G1) or HSV-2 glycoprotein G (G2) allows for the differentiation of an HSV-1 infection from an infection with HSV-2. In the early phase of primary infection the corresponding IgG antibodies are not yet produced. As a rule, IgG antibodies against HSV-1 are formed two to three months after a primary infection with the type 1 herpes simplex virus. IgG-class antibodies against glycoprotein G2 are detectable several weeks after primary infection. This test uses HSV-2 glycoprotein G as coating antigen.
Anti-Measles Virus
The causative agent of measles infection is an RNA virus belonging to the family of paramyxoviridae. Measles are highly contagious; the virus is mainly transmitted via aerosol droplets or contact with infectious secretions. Humans are the only known host, and infected humans constitute the natural reservoir for the mumps virus. The disease occurs all over the world. Routine vaccination with attenuated living virus has proven highly effective in reducing the incidence of measles. In many countries the chains of infection have been interrupted, and most reported cases of measles are imported. Particularly, in parts of Africa and Asia, the vaccination rate is still insufficient and there is considerable incidence of measles virus infection. The incubation period is about 10-14 days. The first symptoms are fever, cough, and conjunctivitis followed by a generalized maculopapular rash. The characteristic measles rash appears two to four days after initial symptoms. Acute measles virus infection is accompanied by immunosuppression, which may last for up to six months, often leading to secondary bacterial or viral infections. These secondary infections are the main reason for the high mortality due to measles worldwide, especially in less developed countries. In patients with a healthy immune system the infection usually proceeds as a self-limiting disease. There is no specific antiviral therapy. Immunity to wild-type measles is believed to confer lifelong immunity. Comorbidities of measles virus infection are various types of neurological disease: post-infectious encephalitis, which affects 0.1 % of measles cases and subacute sclerosing The causative agent of measles infection is an RNA virus belonging to the family of paramyxoviridae. Measles are highly contagious; the virus is mainly transmitted via aerosol droplets or contact with infectious secretions. Humans are the only known host, and infected humans constitute the natural reservoir for the mumps virus.
Anti-Mumps Virus
Mumps (Parotitis epidemica) is an acute viral infection characterized by fever and inflammation of the parotid glands. Common comorbidities are meningitis, encephalitis, deafness and orchitis in young men. Severity increases with age, clinical symptoms are usually more severe in adults and adolescents than children (1). The causative agent of mumps infection is an RNA virus belonging to the family paramyxoviridae (2). Mumps is highly contagious; the virus is mainly transmitted by droplet spread. Humans are the only known host, and infected humans constitute the natural reservoir for the mumps virus. The disease occurs all over the world. Routine vaccination with attenuated living virus has proven highly effective in reducing the incidence of mumps, and is presently used by most developed countries. The common use of a combined measles-mumps and rubella vaccine has further propagated mumps immunization. However, there have been outbreaks of disease in vaccinated populations (3-5), due to increasing vaccine fatigue and insufficient herd immunity, waning immunity after vaccination, or high contact rates (e.g. school children) that facilitate transmission. The incubation period is about 12-25 days (1;2) after which time prodromal symptoms occur; including fever, malaise, myalgia, and headache. After the prodrome, the most common presentation is a painful parotitis, which occurs in up to 70 % of patients. In approximately one third up to almost half of infected individuals the disease proceeds without the characteristic clinical symptoms (2;6)
Anti-Mycoplasma pneumoniae
Mycoplasma pneumoniae is one of the smallest free-living organisms. In addition to Chlamydia and Legionella, M. pneumoniae is one of the primary causes of community-acquired pneumonia.
The serological detection of pathogen-specific antibodies by ELISA is a commonly used method for diagnosing M. pneumoniae infections. Antibodies against M. pneumoniae adhesins are particularly useful because of their high sensitivity and specificity. Adhesins are special surface molecules that help the bacteria stick to the mucosa of the respiratory tract.
The individual detection of IgM, IgG, and IgA antibodies is used to differentiate between primary infections and reinfections. IgM antibodies usually appear seven to ten days after onset of the infection. They are often absent in cases of reinfection. IgG titers increase slowly as the disease progresses, usually reaching a maximum about five weeks after onset of clinical symptoms, after which they slowly decrease. A significant increase in IgG titer within two weeks confirms acute infection. High IgA titers are the best indicator of acute infection in adults; however, low titers of IgA antibodies can persist over longer periods of time.
Anti-Parvovirus
arvovirus B19 is the causative organism of fifth disease (erythema infectiosum). Differentiation between a fresh infection with Parvovirus B19 and exposure that occurred some time ago is of great importance for pregnant patients, since an intrauterine infection can cause severe foetal anaemia.
Approximately ten days after infection IgM antibodies are produced. IgG antibodies appear shortly after the formation of IgM or even simultaneously. In the acute phase of the infection IgG and IgM antibodies bind to linear epitopes of the entire structural protein or to conformational epitopes of the virus capsid. In many cases IgG antibodies preferably directed against conformational epitopes remain after decline of the initial IgM and IgG response, they usually persist for life.
Anti-VZV
The varicella zoster virus (VZV) causes chicken pox and shingles (herpes zoster) and belongs to the family of human pathogenic alpha herpes viruses. After an incubation period of two weeks, patients develop a fever and the typical, itchy chicken pox rash. The infection is usually self-limiting. Herpes zoster is caused by reactivation of the virus, which persists in the ganglia of spinal and cranial nerves. Primary infection with VZV before the twentieth week of pregnancy may cause harm to the unborn child. Neonatal chicken pox infection may also be quite severe. Chicken pox and shingles are usually diagnosed on the basis of clinical symptoms. In cases of complications or infection during pregnancy, serological diagnostics become important. If VZV infection is suspected, IgG, IgM, and IgA antibodies should be tested. IgM antibodies are typical of the acute phase of infection. They are absent or very scarce upon reactivation of the virus (herpes zoster). In such cases, increasing titres of IgA and IgG antibodies are more diagnostically informative. IgG determination is used for documentation of immune status and to confirm successful immunization. The ORGENTEC Anti-VZV IgA and Anti-VZV IgG tests for Alegria® use VZV glycoproteins isolated from virus cell cultures as antigens. Anti-VZV IgG is calibrated against the international WHO reference preparation (NIBSC code W1044). Recombinant glycoprotein E is the antigen in the Anti-VZV IgM Abs. test.
Anti-Yersinia
Yersinia are often only detectable in stool samples for a short time, and cannot be detected at all in joints affected by reactive arthritis. For these reasons, the serological detection of Yersinia-specific antibodies is important. The ORGENTEC tests for Alegria® detect IgA and IgG antibodies against characteristic Yop proteins (Yersinia outer membrane proteins). The Yop proteins are plasmid-encoded virulence factors and are highly specific for all of the Yersinia species that are pathogenic to humans. After initial exposure to the pathogen, IgM antibodies are formed first, soon followed by the IgG and IgA antibodies. IgM antibodies usually disappear after a few weeks. High IgA and IgG antibody titres are indicative of infection in the recent past. IgG antibodies may persist at low levels for years.
Hepatitis B Ag
Hepatitis B virus (HBV) testing plays an important role in detection, classification, and management of HBV disease.
Results of HBV serologic markers can be reported qualitatively or quantitatively as international units (IU) or signal per cutoff (s/c) value. For example, a hepatitis B surface antigen (HBsAg) level of less than 1 s/c is considered negative, while a level of more than 5 s/c is considered positive. Any value between 1 and 5 s/c is indeterminate and should be repeated. For hepatitis B surface antibody (anti-HBs), a level less than 5 mIU is considered negative, while a level more than 12 mIU is considered protective. Any value between 5 and 12 mIU is indeterminate and should be repeated.
There is no standardization between laboratories, and these cutoff values tend to vary between manufacturers. Therefore, results are usually reported as “negative” or “positive.” The laboratory or manufacturer’s insert should be referenced for quantitative measurement, if required.
Hepatitis C
The Hepatitis C virus (HCV) discovered in 1989 using advanced molecular biology techniques, was rapidly found to account for the majority of those patients with non-A non-B hepatitis. HCV represents a major worldwide public health problem requiring global action for the diagnosis, treatment and prevention of this infection (1). HCV is primarily parenterally transmitted through direct blood-to-blood contact between two people: use of unsterilized injection devices and transfusion of unscreened blood or blood products (2). The disease frequently progresses to chronic hepatitis C (80%), exposing patients to a greater risk of hepatic complications such as cirrhosis or hepatocellular carcinoma. (3). The current standard of treatment for HCV is a combination of two drugs: pegylated interferon and ribavirin, but due to the high genetic variability of HCV (4), it is still only partially effective: viral eradication in less than 50% of patients infected with genotype 1 hepatitis C virus against approximately 80% of patients infected with genotype 2 or 3. New herapeutic options are under study to offer more effective and safer personalized treatments (5,6).
Diagnosis of patients infected with HCV can be performed using two categories of virological tests: indirect tests, and direct tests (7). Indirect serological tests are third-generation enzyme immunoassays that detect antibodies to HCV. The antigens used in the tests to detect antibodies are from the structural and non_x0002_structural regions of the HCV (8) (capsid, protein, cofactors, polymerase, etc.). The presence of anti-HCV antibodies indicates that an individual may have been infected with HCV in the past or may have an ongoing HCV infection. To confirm the presence of active HCV infection, a positive serological test can be completed using direct tests (e.g.: molecular assays that detect RNA genomes). The results will be used to guide patient management and determine the optimal duration of treatment.
HIV - 1
Human immunodeficiency virus is the causative agent of acquired immunodeficiency syndrome (AIDS). AIDS was first described in the United States in 1981 and has become one of the leading causes of death worldwide. Despite educational efforts directed towards reducing the transmission of AIDS and increased advancements in treatment, the number of AIDS cases continues to increase.1
Human immunodeficiency virus type 1 (HIV-1) has been identified as the primary cause of acquired immunodeficiency syndrome (AIDS). This retrovirus, a member of the lentivirinae subfamily, is spread by sexual contact, exposure to infected blood or blood products, and perinatal transmission. In 1986, human immunodeficiency virus type 2 (HIV-2) was isolated from AIDS patients in West Africa. These viruses share epitopes of the core proteins, but exhibit little or no cross-reactivity between the envelope glycoproteins.2,3
Comparison of the nucleic acid sequences for HIV-1 and HIV-2 shows approximately 60% homology in the conserved genes, such as gag and pol (encoding core proteins), and 30 to 40% homology in less conserved regions (encoding envelope proteins). HIV-1 has been subdivided into Group M (subtypes A–H) and Group O.4 The routes of transmission of HIV-1 and HIV-2 are the same, however the transmission and the viral replication rate are much lower in HIV-2 infections. Clinical studies have shown that in HIV-2 infections there is a slower disease progression than in HIV-1 infections. In HIV-2 infections there is a slower rate in the decline of CD4 T-cells and reduced viremia. Individuals infected with HIV-2 generally have a better clinical outcome.2,5
HIV - 1/2
Human immunodeficiency virus is the causative agent of acquired immunodeficiency syndrome (AIDS). AIDS was first described in the United States in 1981 and has become one of the leading causes of death worldwide. Despite educational efforts directed towards reducing the transmission of AIDS and increased advancements in treatment, the number of AIDS cases continues to increase.1
Human immunodeficiency virus type 1 (HIV-1) has been identified as the primary cause of acquired immunodeficiency syndrome (AIDS). This retrovirus, a member of the lentivirinae subfamily, is spread by sexual contact, exposure to infected blood or blood products, and perinatal transmission. In 1986, human immunodeficiency virus type 2 (HIV-2) was isolated from AIDS patients in West Africa. These viruses share epitopes of the core proteins, but exhibit little or no cross-reactivity between the envelope glycoproteins.2,3
Comparison of the nucleic acid sequences for HIV-1 and HIV-2 shows approximately 60% homology in the conserved genes, such as gag and pol (encoding core proteins), and 30 to 40% homology in less conserved regions (encoding envelope proteins). HIV-1 has been subdivided into Group M (subtypes A–H) and Group O.4 The routes of transmission of HIV-1 and HIV-2 are the same, however the transmission and the viral replication rate are much lower in HIV-2 infections. Clinical studies have shown that in HIV-2 infections there is a slower disease progression than in HIV-1 infections. In HIV-2 infections there is a slower rate in the decline of CD4 T-cells and reduced viremia. Individuals infected with HIV-2 generally have a better clinical outcome.2,5
HIV Ag/Ab Combo
Human immunodeficiency virus is the causative agent of acquired immunodeficiency syndrome (AIDS). AIDS was first described in the United States in 1981 and has become one of the leading causes of death worldwide. Despite educational efforts directed towards reducing the transmission of AIDS and increased advancements in treatment, the number of AIDS cases continues to increase.1
Human immunodeficiency virus type 1 (HIV-1) has been identified as the primary cause of acquired immunodeficiency syndrome (AIDS). This retrovirus, a member of the lentivirinae subfamily, is spread by sexual contact, exposure to infected blood or blood products, and perinatal transmission. In 1986, human immunodeficiency virus type 2 (HIV-2) was isolated from AIDS patients in West Africa. These viruses share epitopes of the core proteins, but exhibit little or no cross-reactivity between the envelope glycoproteins.2,3
Comparison of the nucleic acid sequences for HIV-1 and HIV-2 shows approximately 60% homology in the conserved genes, such as gag and pol (encoding core proteins), and 30 to 40% homology in less conserved regions (encoding envelope proteins). HIV-1 has been subdivided into Group M (subtypes A–H) and Group O.4 The routes of transmission of HIV-1 and HIV-2 are the same, however the transmission and the viral replication rate are much lower in HIV-2 infections. Clinical studies have shown that in HIV-2 infections there is a slower disease progression than in HIV-1 infections. In HIV-2 infections there is a slower rate in the decline of CD4 T-cells and reduced viremia. Individuals infected with HIV-2 generally have a better clinical outcome.2,5
Measles IgG
The measles virus is a member of the Paramyxoviridae family of viruses, which include parainfluenza virus serotypes 1-4, mumps, respiratory syncytial virus (RSV), and metapneumovirus. The measles virus is one of the most highly contagious infectious diseases among unvaccinated individuals and is transmitted through direct contact with aerosolized droplets or other respiratory secretions from infected individuals. Measles has an incubation period of approximately 8 to 12 days, which is followed by a prodromal phase of high fever, cough, coryza, conjunctivitis, and malaise. Koplik spots may also be apparent on the buccal mucosa and can last for 12 to 72 hours.(1,2) Following this phase, a maculopapular, erythematous rash develops beginning behind the ears and on the forehead and spreads centrifugally to involve the trunk and extremities.
Immunocompromised individuals, pregnant women, and those with nutritional deficiencies are particularly at risk for serious complications following measles infection, which include pneumonia and central nervous system involvement.(1,3)
Following implementation of the national measles vaccination program in 1963, the incidence of measles infection has fallen to fewer than 0.5 cases per 1,000,000 population and the virus is no longer considered endemic in the United States.(4) Measles outbreaks continue to occur in the United States due to exposure of nonimmune individuals or those with waning immunity to infected travelers. The measles outbreak in 2011 throughout Western Europe emphasizes the persistence of the virus in the worldwide population and the continued need for national vaccination programs.(5)
The diagnosis of measles infection is often based on clinical presentation alone. Screening for IgG-class antibodies to measles virus will aid in identifying nonimmune individuals.
Mumps IgG
The mumps virus is a member of the Paramyxoviridae family of viruses, which include parainfluenza virus serotypes 1-4, measles, respiratory syncytial virus (RSV), and metapneumovirus. Mumps is highly infectious among unvaccinated individuals and is typically transmitted through inhalation of infected respiratory droplets or secretions. Following an approximately 2 week incubation period, symptom onset is typically acute with a prodrome of low-grade fever, headache, and malaise.(1,2) Painful enlargement of the salivary glands, the hallmark of mumps, occurs in approximately 60% to 70% of infections and in 95% of patients with symptoms. Testicular pain (orchitis) occurs in approximately 15% to 30% of postpubertal men and abdominal pain (oophoritis) is found in 5% of postpubertal women.(1) Other complications include mumps-associated pancreatitis (<5% of cases) and central nervous system disease (meningitis <10% and encephalitis <1%).
Widespread routine immunization of infants with attenuated mumps virus has dramatically decreased the number of reported mumps cases in the United States. However, outbreaks continue to occur, indicating persistence of the virus in the general population.
Laboratory diagnosis of mumps is typically accomplished by detection of IgM- and IgG-class antibodies to the mumps virus. However, due to the widespread mumps vaccination program, in clinically suspected cases of acute mumps infection, serologic testing should be supplemented with virus isolation in culture or detection of viral nucleic acid by polymerase chain reaction (PCR) in throat, saliva, or urine specimens.
Syphilis TP
Syphilis is primarily transmitted via sexual contact, but can also be transmitted from mother to fetus. Syphilis is caused by the spirochete T. pallidum, which has never been successfully cultured in artificial media. Syphilis infections are classified into early (infectious) and late (non-infectious) stages. Early syphilis may be further divided into primary, secondary, and early latent syphilis. The signs and symptoms of syphilis are numerous; before the advent of serological testing, precise diagnosis was very difficult. In fact, the disease was often confused with other diseases, particularly in its tertiary stage. If not treated, syphilis can cause serious effects such as damage to the heart, aorta, brain, eyes, and bones. In some cases these effects can be fatal. Therefore, the serological diagnosis of syphilis is very important.1,2
The serological diagnosis of syphilis is classified into two groups: nontreponemal tests and treponemal tests. Nontreponemal tests, which include venereal disease research laboratory (VDRL) and rapid plasma reagin (RPR) tests, detect antibodies formed by the host in response to lipid material released from damaged host cells as well as to lipoprotein-like material released from the spirochete. Treponemal tests detect specific treponemal antibodies, and the techniques used include agglutination (T. pallidum hemagglutination [TPHA], T. pallidum particle agglutination [TPPA]), immunoassay (enzyme immunoassay [EIA] or chemiluminescent immunoassay [CLIA]), immunofluorescence (fluorescent treponemal antibody absorption [FTA-ABS]), and immunoblotting. Nontreponemal tests have poor sensitivity and specificity, and recombinant antigen-based treponemal tests have higher sensitivity and specificity than native antigen-based treponemal tests.3,
TORCH and Special ID
A TORCH screen is a panel of tests for detecting infections in pregnant women. Infections may be passed on to a fetus during pregnancy. Early detection and treatment of an infection can prevent complications in newborns.
TORCH, sometimes referred to as TORCHS, is an acronym of the infections covered in the screening:
- toxoplasmosis
- other (HIV, hepatitis viruses, varicella, parvovirus)
- rubella (German measles)
- cytomegalovirus
- herpes simplex
- syphilis
Varicella - Zoster IgG
Varicella-zoster virus (VZV), a herpesvirus, causes 2 distinct exanthematous (rash-associated) diseases: chickenpox (varicella) and shingles (herpes zoster). Chickenpox is a highly contagious, though typically benign disease, usually contracted during childhood. Chickenpox is characterized by a dermal vesiculopustular rash that develops in successive crops approximately 10 to 21 days following exposure.(1) Although primary infection with VZV results in immunity and protection from subsequent infection, VZV remains latent within sensory dorsal root ganglia and upon reactivation, manifests as herpes zoster or shingles. During reactivation, the virus migrates along neural pathways to the skin, producing a unilateral rash, usually limited to a single dermatome. Shingles is an extremely painful condition typically occurring in older nonimmune adults or those with waning immunity to VZV and in patients with impaired cellular immunity.(2)
Individuals at risk for severe complications following primary VZV infection include pregnant women, in whom the virus may spread through the placenta to the fetus causing congenital disease in the infant. Additionally, immunosuppressed patients are at risk for developing severe VZV-related complications, which include cutaneous disseminated disease and visceral organ involvement.(2,3)
Serologic screening for IgG-class antibodies to VZV will aid in identifying nonimmune individuals. The presence of IgM-class antibodies to VZV is suggestive of acute or recent infection however results should be correlated with clinical presentation.
Intact PTH
Parathyroid hormone (PTH), produced by the parathyroid gland, is the major circulating factor regulating extracellular calcium concentration. Abnormally low ionized calcium concentrations trigger the secretion of PTH. The PTH molecules bind to type 1 parathyroid hormone receptors in target tissues and initiate a sequence of reactions that results in an increase in extracellular calcium concentrations. PTH stimulates osteoclastic bone resorption resulting in the release of calcium from bone. PTH stimulates transcellular calcium reabsorption from the renal tubules and stimulates the kidney to produce 1,25-dihydroxyvitamin D which acts on the intestines to increase calcium reabsorption.1,2,3 In most clinical conditions, rising levels of extracellular calcium will suppress PTH secretion through a negative feedback mechanism.4
Parathyroid hormone increases the rate of bone metabolism. Depending on the age of the patient, the bones involved, and the concentrations of the hormone in circulation over time, the effect on the bone can be either catabolic or anabolic. Consistently high concentrations of parathyroid hormone generally have a catabolic effect and intermittent slightly elevated concentrations have an anabolic effect.
The intact PTH peptide (MW ~9425) consists of 84 amino acids that are sequenced and designated according to reactivity. The N-terminal or amino-terminal 1-34 region of the intact PTH molecule is biologically active. This region of the molecule contains the amino acid sequence that enables PTH to bind to the parathyroid hormone receptors in target tissues and regulate extracellular calcium concentrations. The middle and carboxy-terminal 35-84 region of the intact PTH molecule is biologically inert but possesses immunological reactivity.5,6 The intact PTH molecule undergoes intra- and extra-glandular proteolytic modifications that produce PTH fragments. Circulating PTH is heterogeneous, existing as both the intact PTH and PTH fragments. The PTH peptides have different rates of clearance from the circulation. Intact PTH has a half-life that is less then 4 minutes and is cleared by the kidney and liver. The Kupffer cells in the liver are responsible for cleaving the intact molecule into fragments and releasing them into the circulation. Very little, if any, of the amino-terminal PTH fragments are detected in circulation. The middle and carboxy-terminal PTH fragments vary in size, have longer half-lives, and are primarily cleared in the kidney by glomerular filtration. Under normal conditions, there is a greater relative concentration of circulating middle and carboxy-terminal PTH fragments. In renal insufficiency where glomerular filtration is impaired, the concentration of middle and carboxy-terminal PTH fragments is increased. The ratio of the circulating concentrations of intact PTH to middle and carboxy-terminal PTH can vary between individuals, particularly in patients with chronic renal failure.1,2,5,6
Quantification of circulating intact PTH assists in the differential diagnosis of hypercalcemia and hypocalcemia. In conjunction with the measurement of ionized calcium, intact PTH evaluations can be used to distinguish between patients with hyperparathyroidism, hypoparathyroidism, or hypercalcemia of malignancy. The diagnosis of primary hyperparathyroidism, a common cause of hypercalcemia, is confirmed by elevated ionized calcium concentrations and elevated parathyroid hormone concentrations. Intact PTH levels are also used to assess and manage other metabolic bone disorders, including osteoporosis and renal osteodystrophy.1,2,7,8 The measurement of intact PTH using two-site immunoassays provides a more accurate assessment of parathyroid tissue secretary status, especially in patients with renal impairment.9
25 oh Vitamin D total
Vitamin D helps your body absorb calcium and maintain strong bones throughout your entire life. Your body produces vitamin D when the sun’s UV rays contact your skin. Other good sources of the vitamin include fish, eggs, and fortified dairy products. It’s also available as a dietary supplement.
Vitamin D must go through several processes in your body before your body can use it. The first transformation occurs in the liver. Here, your body converts vitamin D to a chemical known as 25-hydroxyvitamin D, also called calcidiol.
The 25-hydroxy vitamin D test is the best way to monitor vitamin D levels. The amount of 25-hydroxyvitamin D in your blood is a good indication of how much vitamin D your body has. The test can determine if your vitamin D levels are too high or too low.
The test is also known as the 25-OH vitamin D test and the calcidiol 25-hydroxycholecalcifoerol test. It can be an important indicator of osteoporosis (bone weakness) and rickets (bone malformation).
Vitamin D
Vitamin D is a steroid hormone involved in the intestinal absorption of calcium and the regulation of calcium homeostasis. Vitamin D is essential for the formation and maintenance of strong, healthy bones.Vitamin D deficiency can result from inadequate exposure to the sun, inadequate alimentary intake, decreased absorption, abnormal metabolism, or vitamin D resistance.1 Recently, many chronic diseases such as cancer,2–4 high blood pressure,5 osteoporosis,6,7 and several autoimmune diseases8–10 have been linked to vitamin D deficiency. Whether consumed or produced, both forms of vitamin D (D2 and D3) are metabolized by the liver to 25(OH)vitamin D, and then converted in the liver or kidney into 1,25-dihydroxyvitamin D.11 Vitamin D metabolites are bound to a carrier protein in the plasma and distributed throughout the body. The most reliable clinical indicator of vitamin D status is 25(OH)vitamin D because serum and plasma 25(OH)vitamin D levels reflect the body’s storage levels of vitamin D, and 25(OH)vitamin D correlates with the clinical symptoms of vitamin D deficiency.
PTH (1-84)
The four-sectioned parathyroid glands are located in your neck, at the edge of the thyroid gland. They’re responsible for regulating calcium, vitamin D, and phosphorus levels in your blood and bones.
The parathyroid glands release a hormone called parathyroid hormone (PTH), also known as parathormone. This hormone helps regulate calcium levels in the blood.
Calcium imbalances in the blood may be a sign of parathyroid gland or PTH issues. Calcium levels in the blood signal the parathyroid glands to release or suppress PTH.
When calcium levels are low, the parathyroid glands increase PTH production. When calcium levels are high, the glands slow down the secretion of PTH.
Some symptoms and medical conditions may cause your doctor to measure how much PTH is in your blood. Because of the relationship between calcium and PTH in the blood, both are often tested at the same time.
Ferritin
Ferritin is the most common type of iron storage in the human body (1). Its molecules can be found in the cytoplasm of the reticuloendothelial system, specifically in the liver and spleen. Ferritin has the shape of a hollow spherical protein envelope composed of 24 protein sub-units. The iron is situated in the center of the molecule in the form of ferric hydroxyphosphate. This molecule may contain as many as 4,500 iron atoms (2). Iron deficiency anemia is a common ailment which may be caused by insufficient iron intake, pregnancy, hemodialysis or blood donation (3). The drop in serum ferritin levels can indicate an iron deficiency prior to the appearance of anemia. Detection of insufficient ferritin levels therefore enables anticipated treatment (4). Furthermore, iron overload is characteristic of illnesses such as thalassemia and sideroblastic anemia. In such cases, the measurement of serum ferritin levels contributes to diagnosis and patient monitoring (5, 6). The level of serum ferritin acts as an indicator of the quantities of iron in the human body (7,8). It is also closely correlated to the level of iron in the bone marrow. Quantitative data are obtained from the determination of serum ferritin concentration, thus avoiding the need for bone marrow biopsy, which is a more invasive technique.
BRAHMS PCT
Procalcitonin (ProCT) is a 116-amino acid precursor of calcitonin (CT). ProCT is processed to an N-terminal 57 amino acid peptide (CT [32-amino acids] and a 21-amino acid C-terminal peptide, catacalcin [CCP-1]). Expression of this group of peptides is normally limited to thyroid C cells and, to a small extent, other neuroendocrine cells. CT is the only hormonally active of these peptides. CT is secreted by C cells in response to hypercalcemia and inhibits bone resorption by osteoclasts, minimizing oscillations in serum calcium and calcium loss.
During severe systemic inflammation, in particular related to bacterial infection, the tissue-specific control of CT-related peptides expression breaks down and ProCT and CCP-1 (referred collectively to as ProCT) are secreted in large quantities by many tissues. CT levels do not change.
Noninfectious inflammatory stimuli need to be extremely severe to result in ProCT elevations, making it a more specific marker for severe infections than most other inflammatory markers (cytokines, interleukins, and acute-phase reactants). ProCT elevations are also more sustained than those of most other markers and occur in neutropenic patients. This reduces the risk of false-negative results.
ProCT becomes detectable within 2 to 4 hours after a triggering event and peaks by 12 to 24 hours. ProCT secretion parallels closely the severity of the inflammatory insult, with higher levels associated with more severe disease and declining levels with resolution of illness. In the absence of an ongoing stimulus, ProCT is eliminated with a half-life of 24 to 35 hours, making it suitable for serial monitoring. Finally, the dependence of sustained ProCT elevations on ongoing inflammatory stimuli allows identification of secondary septic events in conditions that can result in noninfectious ProCT elevations, such as cardiac surgery, severe trauma, severe burns, and multiorgan failure. ProCT levels should fall at a predictable pace in the absence of secondary infection.
BLOOD CULTURE IDENTIFICATION
The Blood Culture Identification (BCID) Panel is a qualitative multiplexed nucleic acid-based in vitro diagnostic test intended for use with FilmArray systems. The FilmArray BCID Panel is capable of simultaneous detection and identification of multiple bacterial and yeast nucleic acids and select genetic determinants of antimicrobial resistance. The FilmArray BCID Panel assay is performed directly on blood culture samples identified as positive by a continuous monitoring blood culture system. Results are intended to be interpreted in conjunction with Gram stain results.
The following gram-positive bacteria, gram-negative bacteria, and yeast are identified using the FilmArray BCID Panel: Enterococci, Listeria monocytogenes, Staphylococci (including specific differentiation of Staphylococcus aureus), Streptococci (with specific differentiation of Streptococcus agalactiae, Streptococcus pneumoniae, and Streptococcuspyogenes), Acinetobacter baumannii, Enterobacteriaceae (including specific differentiation of the Enterobacter cloacae complex, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus, and Serratia marcescens), Haemophilus influenzae, Neisseria meningitidis (encapsulated), Pseudomonas aeruginosa, Candida albicans, Candida glabrata, Candida krusei, Candida parapsilosis, and Candida tropicalis.
The FilmArray BCID Panel also contains assays for the detection of genetic determinants of resistance to methicillin (mecA), vancomycin (vanA and vanB), and carbapenems (blaKPC) to aid in the identification of potentially antimicrobial resistant organisms in positive blood culture samples. The antimicrobial resistance gene detected may or may not be associated with the agent responsible for disease. Negative results for these select antimicrobial resistance gene assays do not indicate susceptibility, as multiple mechanisms of resistance to methicillin, vancomycin, and carbapenems exist.
GASTROINTESTINAL PANEL
The Gastrointestinal (GI) Panel is a qualitative multiplexed nucleic acid-based in vitro diagnostic test intended for use with FilmArray systems. The FilmArray GI Panel is capable of the simultaneous detection and identification of nucleic acids from multiple bacteria, viruses, and parasites directly from stool samples in Cary Blair transport media obtained from individuals with signs and/or symptoms of gastrointestinal infection. The following bacteria (including several diarrheagenic E. coli/Shigella pathotypes), parasites, and viruses are identified using the FilmArray GI Panel: Campylobacter (C. jejuni/C. coli/C. upsaliensis) , Clostridium difficile (C. difficile) toxin A/B, Plesiomonas shigelloides, Salmonella, Vibrio (V. parahaemolyticus/V. vulnificus/ V. cholerae), including specific identification of Vibrio cholerae, Yersinia enterocolitica, Enteroaggregative Escherichia coli (EAEC) , Enteropathogenic Escherichia coli (EPEC) , Enterotoxigenic Escherichia coli (ETEC) lt/st, Shiga-like toxin-producing Escherichia coli (STEC) stx1/stx2 (including specific identification of the E. coli O157 serogroup within STEC) , Shigella/ Enteroinvasive Escherichia coli (EIEC) , Cryptosporidium, Cyclospora cayetanensis, Entamoeba histolytica, Giardia lamblia (also known as G. intestinalis and G. duodenalis) Adenovirus F 40/41 , Astrovirus , Norovirus GI/GII , Rotavirus A , Sapovirus (Genogroups I, II, IV, and V).
MENINGITIS/ENCEPHALITIS PANEL
The Meningitis/Encephalitis (ME) Panel is a qualitative multiplexed nucleic acid-based in vitro diagnostic test intended for use with FilmArray systems. The FilmArray ME Panel is capable of simultaneous detection and identification of multiple bacterial, viral, and yeast nucleic acids directly from cerebrospinal fluid (CSF) specimens obtained via lumbar puncture from individuals with signs and/or symptoms of meningitis and/or encephalitis. The following organisms are identified using the FilmArray ME Panel: (Bacteria) Escherichia coli K1, Haemophilus influenzae, Listeria monocytogenes, Neisseria meningitidis (encapsulated), Streptococcus agalactiae, Streptococcus pneumoniae, (Viruses) Cytomegalovirus, Enterovirus, Herpes simplex virus 1, Herpes simplex virus 2, Human herpesvirus 6, Human parechovirus, Varicella zoster virus, (Yeast) Cryptococcus neoformans/gattii.
PNEUMONIA PANEL
The Pneumonia Panel is a multiplexed nucleic acid test intended for use with FilmArray®, FilmArray® 2.0, or FilmArray® Torch systems for the simultaneous detection and identification of multiple respiratory viral and bacterial nucleic acids, as well as select antimicrobial resistance genes, in sputum-like specimens (induced or expectorated sputum, or endotracheal aspirates) or bronchoalveolar lavage (BAL)-like specimens (BAL or mini-BAL) obtained from individuals suspected of lower respiratory tract infection. The following bacteria are reported semi-quantitatively with bins representing approximately 10^4, 10^5, 10^6, or ≥10^7 genomic copies of bacterial nucleic acid per milliliter (copies/mL) of specimen, to aid in estimating relative abundance of nucleic acid from these common bacteria within a specimen: Acinetobacter calcoaceticus-baumannii complex, Klebsiella oxytoca, Serratia marcescens, Enterobacter cloacae complex Klebsiella pneumoniae group Staphylococcus aureus, Escherichia coli Moraxella catarrhalis Streptococcus agalactiae, Haemophilus influenzae Proteus spp. Streptococcus pneumoniae, Klebsiella aerogenes, Pseudomonas aeruginosa ,Streptococcus pyogenes. The following atypical bacteria: Chlamydia pneumoniae, Legionella pneumophila, Mycoplasma pneumoniae, Chlamydia pneumoniae Legionella pneumophila Mycoplasma pneumoniae, Viruses: Adenovirus Human Rhinovirus/Enterovirus Parainfluenza Virus, and Antimicrobial Resistance Genes: CTX-M NDM mecA/C, MREJ, IMP, OXA-48, KPC VIM are reported qualitatively.
RESPIRATORY 2.1 PLUS PANEL
The BioFire Respiratory Panel 2.1 (RP2.1) is a multiplexed nucleic acid test intended for the simultaneous qualitative detection and differentiation of nucleic acids from multiple viral and bacterial respiratory organisms, including nucleic acid from Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), in nasopharyngeal swabs (NPS) obtained from individuals suspected of COVID-19 by their healthcare provider. The BioFire Respiratory Panel 2.1 (RP2.1) is intended for the detection and differentiation of nucleic acid from SARS CoV-2 and the following organism types and subtypes identified using the BioFire RP2.1. Viruses includes Adenovirus, Coronavirus 229E, Coronavirus HKU1, Coronavirus NL63 , Coronavirus OC43, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Human Metapneumovirus, Human Rhinovirus/Enterovirus, Influenza A, including subtypes H1, H3 and H1-2009, Influenza B, Parainfluenza Virus 1, Parainfluenza Virus 2, Parainfluenza Virus 3, Parainfluenza Virus 4, Respiratory Syncytial Virus. The bacteria includes Bordetella parapertussis, Bordetella pertussis, Chlamydia pneumoniae, and Mycoplasma pneumoniae.
AFP
Alpha-fetoprotein (AFP) is a glycoprotein that is produced in early fetal life by the liver and by a variety of tumors including hepatocellular carcinoma, hepatoblastoma, and nonseminomatous germ cell tumors of the ovary and testis (eg, yolk sac and embryonal carcinoma). Most studies report elevated AFP concentrations in approximately 70% of patients with hepatocellular carcinoma. Elevated AFP concentrations are found in 50% to 70% of patients with nonseminomatous testicular tumors.
AFP is elevated during pregnancy. Persistence of AFP in the mother following birth is a rare hereditary condition.(2) Neonates have markedly elevated AFP levels (>100,000 ng/mL) that rapidly fall to below 100 ng/mL by 150 days and gradually return to normal over their first year.
Concentrations of AFP above the reference range also have been found in the serum of patients with benign liver disease (eg, viral hepatitis, cirrhosis), gastrointestinal tract tumors, and along with carcinoembryonic antigen, in ataxia telangiectasia.
The biological half-life of AFP is approximately 5 days.
ANDROSTENEDIONE
Androstenedione is secreted predominately by the adrenal gland and production is at least partly controlled by adrenocorticotropic hormone (ACTH). It is also produced ACTH-independent in the testes and ovaries from adrenal-secreted dehydroepiandrosterone sulfate (DHEA-S). Androstenedione is a crucial sex-steroid precursor.
Androstenedione production during life mimics the pattern of other androgen precursors. Fetal serum concentrations increase throughout embryonal development and peak near birth at approximately young adult levels. Levels then fall rapidly during the first year of life to low prepubertal values. With the onset of adrenarche, androstenedione rises gradually, a process that accelerates with the onset of puberty, reaching adult levels around age 18. Adrenarche is a poorly understood phenomenon peculiar to higher primates that is characterized by a gradual rise in adrenal androgen production. It precedes puberty, but is not causally linked to it. Early adrenarche is not associated with early puberty, or with any reduction in final height, or overt androgenization, and is generally regarded as a benign condition not requiring intervention. However, girls with early adrenarche may be at increased risk of polycystic ovarian syndrome as adults, and some boys may develop early penile enlargement.
Elevated androstenedione levels can cause symptoms or signs of hyperandrogenism in women. Men are usually asymptomatic, but through peripheral conversion of androgens to estrogens can occasionally experience mild symptoms of estrogen excess, such as gynecomastia.
Most mild-to-moderate elevations in androstenedione are idiopathic. However, pronounced elevations of androstenedione may be indicative of androgen-producing adrenal or gonadal tumors.
In children, adrenal and gonadal tumors are uncommon, but many forms of congenital adrenal hyperplasia can increase serum androstenedione concentrations. Diagnosis always requires measurement of other androgen precursors (eg, OHPG, 17-alpha-hydroxypregnenolone, and DHEA-S) and cortisol, in addition to androstenedione.
AMH
Antimullerian hormone (AMH), also known as mullerian-inhibiting substance, is a dimeric glycoprotein hormone belonging to the transforming growth factor-beta family. It is produced by Sertoli cells of the testis in males and by ovarian granulosa cells in females. Expression during male fetal development prevents the mullerian ducts from developing into the uterus, resulting in development of the male reproductive tract. In the absence of AMH, the mullerian ducts and structures develop into the female reproductive tract. AMH serum concentrations are elevated in males under 2 years old and then progressively decrease until puberty, when there is a sharp decline. In females, serum AMH concentrations are very low at birth, peaking after puberty, decrease progressively thereafter with age, and become undetectable at menopause.
Because of the gender differences in AMH concentrations, its changes in circulating concentrations with sexual development, and its specificity for Sertoli and granulosa cells, measurement of AMH has utility in the assessment of gender, gonadal function, fertility, and as a gonadal tumor marker.
In females, AMH is considered an ovarian reserve marker. It correlates with the primordial follicle pool, has an inverse correlation with chronologic age, predicts ovarian response in assisted reproductive therapy, and has been suggested to be predictive of the timing of the onset of menopause. In contrast to other markers of ovarian reserve that show significant fluctuations during the menstrual cycle, serum AMH concentrations have been shown to be relatively stable. Females with higher concentrations of AMH have a better response to ovarian stimulation and tend to produce more retrievable oocytes than females with low or undetectable AMH. Females at risk of ovarian hyperstimulation syndrome after gonadotropin administration can have significantly elevated AMH concentrations. Polycystic ovarian syndrome can elevate serum AMH concentrations because it is associated with the presence of large numbers of small follicles.
AMH measurements are commonly used to evaluate testicular presence and function in infants with intersex conditions or ambiguous genitalia and to distinguish between cryptorchidism and anorchia in males.
Serum AMH concentrations are increased in some patients with ovarian granulosa cell tumors, which comprise approximately 10% of ovarian tumors. AMH, along with related tests including inhibin A and B (INHA / Inhibin A, Tumor Marker, Serum; INHB / Inhibin B, Serum; INHAB / Inhibin A and B, Tumor Marker, Serum), estradiol (EEST / Estradiol, Serum), and cancer antigen 125 (CA25 / Cancer Antigen 125 [CA 125], Serum), can be useful for diagnosing and monitoring these patients.
DHEAS
Antimullerian hormone (AMH), also known as mullerian-inhibiting substance, is a dimeric glycoprotein hormone belonging to the transforming growth factor-beta family. It is produced by Sertoli cells of the testis in males and by ovarian granulosa cells in females. Expression during male fetal development prevents the mullerian ducts from developing into the uterus, resulting in development of the male reproductive tract. In the absence of AMH, the mullerian ducts and structures develop into the female reproductive tract. AMH serum concentrations are elevated in males under 2 years old and then progressively decrease until puberty, when there is a sharp decline. In females, serum AMH concentrations are very low at birth, peaking after puberty, decrease progressively thereafter with age, and become undetectable at menopause.
Because of the gender differences in AMH concentrations, its changes in circulating concentrations with sexual development, and its specificity for Sertoli and granulosa cells, measurement of AMH has utility in the assessment of gender, gonadal function, fertility, and as a gonadal tumor marker.
In females, AMH is considered an ovarian reserve marker. It correlates with the primordial follicle pool, has an inverse correlation with chronologic age, predicts ovarian response in assisted reproductive therapy, and has been suggested to be predictive of the timing of the onset of menopause. In contrast to other markers of ovarian reserve that show significant fluctuations during the menstrual cycle, serum AMH concentrations have been shown to be relatively stable. Females with higher concentrations of AMH have a better response to ovarian stimulation and tend to produce more retrievable oocytes than females with low or undetectable AMH. Females at risk of ovarian hyperstimulation syndrome after gonadotropin administration can have significantly elevated AMH concentrations. Polycystic ovarian syndrome can elevate serum AMH concentrations because it is associated with the presence of large numbers of small follicles.
AMH measurements are commonly used to evaluate testicular presence and function in infants with intersex conditions or ambiguous genitalia and to distinguish between cryptorchidism and anorchia in males.
Serum AMH concentrations are increased in some patients with ovarian granulosa cell tumors, which comprise approximately 10% of ovarian tumors. AMH, along with related tests including inhibin A and B (INHA / Inhibin A, Tumor Marker, Serum; INHB / Inhibin B, Serum; INHAB / Inhibin A and B, Tumor Marker, Serum), estradiol (EEST / Estradiol, Serum), and cancer antigen 125 (CA25 / Cancer Antigen 125 [CA 125], Serum), can be useful for diagnosing and monitoring these patients.
ENHANCED ESTRADIOL
Estrogens are involved in development and maintenance of the female phenotype, germ cell maturation, and pregnancy. They also are important for many other, nongender-specific processes, including growth, nervous system maturation, bone metabolism/remodeling, and endothelial responsiveness. The 2 major biologically active estrogens in nonpregnant humans are estrone (E1) and estradiol (E2). A third bioactive estrogen, estriol (E3), is the main pregnancy estrogen, but plays no significant role in nonpregnant women or men.
E2 is produced primarily in ovaries and testes by aromatization of testosterone. Small amounts are produced in the adrenal glands and some peripheral tissues, most notably fat. By contrast, most of the circulating E1 is derived from peripheral aromatization of androstenedione (mainly adrenal). E2 and E1 can be converted into each other, and both can be inactivated via hydroxylation and conjugation. E2 demonstrates 1.25 to 5 times the biological potency of E1. E2 circulates at 1.5 to 4 times the concentration of E1 in premenopausal, nonpregnant women. E2 levels in men and postmenopausal women are much lower than in nonpregnant women, while E1 levels differ less, resulting in a reversal of the premenopausal E2:E1 ratio. E2 levels in premenopausal women fluctuate during the menstrual cycle. They are lowest during the early follicular phase. E2 levels then rise gradually until 2 to 3 days before ovulation, at which stage they start to increase much more rapidly and peak just before the ovulation-inducing luteinizing hormone (LH)/follicle stimulating hormone (FSH) surge at 5 to 10 times the early follicular levels. This is followed by a modest decline during the ovulatory phase. E2 levels then increase again gradually until the midpoint of the luteal phase and, thereafter, decline to trough, early follicular levels.
Measurement of serum E2 forms an integral part of the assessment of reproductive function in females, including assessment of infertility, oligo-amenorrhea, and menopausal status. In addition, it is widely used for monitoring ovulation induction, as well as during preparation for in vitro fertilization. For these applications E2 measurements with modestly sensitive assays suffice. However, extra sensitive E2 assays, simultaneous measurement of E1, or both are needed in a number of other clinical situations. These include inborn errors of sex steroid metabolism, disorders of puberty, estrogen deficiency in men, fracture risk assessment in menopausal women, and increasingly, therapeutic drug monitoring, either in the context of low-dose female hormone replacement therapy or antiestrogen treatment.
FREE B-HCG
Human chorionic gonadotropin (hCG) is a glycoprotein hormone (molecular weight: MW approximately 36,000 Dalton: Da) consisting of 2 noncovalently bound subunits. The alpha subunit (92-amino acids; "naked" protein MW 10,205 Da) is essentially identical to that of luteinizing hormone (LH), follicle-stimulating hormone, and thyrotropin (previously known as thyroid-stimulating hormone: TSH). The alpha subunit is essential for receptor transactivation. The different beta subunits of the above hormones are transcribed from separate genes, show less homology, and convey the receptor-specificity of the dimeric hormones. The chorionic gonadotropin, beta gene (coding for a 145-amino acid, "naked" protein MW 15,531 Da, glycosylated subunit MW approximately 22,500 Da) is highly homologous to the beta subunit of LH and acts through the same receptor. However, while LH is a classical tropic pituitary hormone, hCG does not usually circulate in significant concentrations. In pregnant primates (including humans) it is synthesized in the placenta and maintains the corpus luteum and, hence, progesterone production, during the first trimester. Thereafter, the placenta produces steroid hormones, diminishing the role of hCG. hCG concentrations fall, leveling off around week 20, significantly above prepregnancy levels. After delivery, miscarriage, or pregnancy termination, hCG falls with a half-life of 24 to 36 hours, until prepregnancy levels are reached.
Outside of pregnancy, hCG may be secreted by abnormal germ cell, placental, or embryonal tissues, in particular seminomatous and nonseminomatous testicular tumors; ovarian germ cell tumors; gestational trophoblastic disease (GTD: hydatidiform mole and choriocarcinoma); and benign or malignant nontesticular teratomas. Rarely, other tumors including hepatic, neuroendocrine, breast, ovarian, pancreatic, cervical, and gastric cancers may secrete hCG, usually in relatively modest quantities.
During pathological hCG production, the highly coordinated secretion of alpha and beta subunits of hCG may be disturbed. In addition to secreting intact hCG, tumors may produce disproportionate quantities of free alpha-subunits or, more commonly, free beta-subunits. Assays that detect both intact hCG and free beta-hCG, including this assay, tend to be more sensitive in detecting hCG-producing tumors.
With successful treatment of hCG-producing tumors, hCG levels should fall with a half-life of 24 to 36 hours, and eventually return to the reference range
FSH
Luteinizing hormone (LH) is a glycoprotein hormone consisting of 2 noncovalently bound subunits (alpha and beta). Gonadotropin-releasing hormone from the hypothalamus controls the secretion of the gonadotropins, follicle-stimulating hormone (FSH), and LH from the anterior pituitary.
The menstrual cycle is divided by a midcycle surge of both FSH and LH into a follicular phase and a luteal phase.
FSH appears to control gametogenesis in both males and females.
HCG
Human chorionic gonadotropin (hCG) is a glycoprotein hormone (molecular weight: MW approximately 36,000 Dalton: Da) consisting of 2 noncovalently bound subunits. The alpha subunit (92-amino acids; "naked" protein MW 10,205 Da) is essentially identical to that of luteinizing hormone (LH), follicle-stimulating hormone, and thyrotropin (previously known as thyroid-stimulating hormone: TSH). The alpha subunit is essential for receptor transactivation. The different beta subunits of the above hormones are transcribed from separate genes, show less homology, and convey the receptor-specificity of the dimeric hormones. The chorionic gonadotropin, beta gene (coding for a 145-amino acid, "naked" protein MW 15,531 Da, glycosylated subunit MW approximately 22,500 Da) is highly homologous to the beta subunit of LH and acts through the same receptor. However, while LH is a classical tropic pituitary hormone, hCG does not usually circulate in significant concentrations. In pregnant primates (including humans) it is synthesized in the placenta and maintains the corpus luteum and, hence, progesterone production, during the first trimester. Thereafter, the placenta produces steroid hormones, diminishing the role of hCG. hCG concentrations fall, leveling off around week 20, significantly above prepregnancy levels. After delivery, miscarriage, or pregnancy termination, hCG falls with a half-life of 24 to 36 hours, until prepregnancy levels are reached.
Outside of pregnancy, hCG may be secreted by abnormal germ cell, placental, or embryonal tissues, in particular seminomatous and nonseminomatous testicular tumors; ovarian germ cell tumors; gestational trophoblastic disease (GTD: hydatidiform mole and choriocarcinoma); and benign or malignant nontesticular teratomas. Rarely, other tumors including hepatic, neuroendocrine, breast, ovarian, pancreatic, cervical, and gastric cancers may secrete hCG, usually in relatively modest quantities.
During pathological hCG production, the highly coordinated secretion of alpha and beta subunits of hCG may be disturbed. In addition to secreting intact hCG, tumors may produce disproportionate quantities of free alpha-subunits or, more commonly, free beta-subunits. Assays that detect both intact hCG and free beta-hCG, including this assay, tend to be more sensitive in detecting hCG-producing tumors.
With successful treatment of hCG-producing tumors, hCG levels should fall with a half-life of 24 to 36 hours, and eventually return to the reference range
LH
Luteinizing hormone (LH) is a glycoprotein hormone consisting of 2 non-covalently bound subunits (alpha and beta). The alpha subunit of LH, follicle-stimulating hormone (FSH), thyrotropin (formerly known as thyroid-stimulating hormone: TSH), and human chorionic gonadotropin (hCG) are identical and contain 92 amino acids. The beta subunits of these hormones vary and confer the hormones' specificity. LH has a beta subunit of 121 amino acids and is responsible for interaction with the LH receptor. This beta subunit contains the same amino acids in sequence as the beta subunit of hCG, and both stimulate the same receptor; however, the hCG-beta subunit contains an additional 24 amino acids, and the hormones differ in the composition of their sugar moieties. Gonadotropin-releasing hormone from the hypothalamus controls the secretion of the gonadotropins, FSH, and LH, from the anterior pituitary.
In both males and females, LH is essential for reproduction. In females, the menstrual cycle is divided by a midcycle surge of both LH and FSH into a follicular phase and a luteal phase. This "LH surge" triggers ovulation thereby not only releasing the egg, but also initiating the conversion of the residual follicle into a corpus luteum that, in turn, produces progesterone to prepare the endometrium for a possible implantation. LH is necessary to maintain luteal function for the first 2 weeks. In case of pregnancy, luteal function will be further maintained by the action of hCG (a hormone very similar to LH) from the newly established pregnancy. LH supports thecal cells in the ovary that provide androgens and hormonal precursors for estradiol production. LH in males acts on testicular interstitial cells of Leydig to cause increased synthesis of testosterone.
PAPP-A
PAPP-A, a large glycoprotein complex predominantly produced by the placenta, has been implicated in the autocrine and paracrine control of trophoblast invasion of the decidua.145 Maternal serum PAPP-A has been shown to be relatively low during the first trimester of pregnancies complicated by preeclampsia.146 Based on this association, several groups of investigators have examined the value of low maternal serum levels of PAPP-A in the prediction of preeclampsia.
PIGF
Clinical manifestations of immediate hypersensitivity (allergic) diseases are caused by the release of proinflammatory mediators (histamine, leukotrienes, and prostaglandins) from immunoglobulin E (IgE)-sensitized effector cells (mast cells and basophils) when cell-bound IgE antibodies interact with allergen.
In vitro serum testing for IgE antibodies provides an indication of the immune response to allergen(s) that may be associated with allergic disease.
The allergens chosen for testing often depend upon the age of the patient, history of allergen exposure, season of the year, and clinical manifestations. In individuals predisposed to develop allergic disease(s), the sequence of sensitization and clinical manifestations proceed as follows: eczema and respiratory disease (rhinitis and bronchospasm) in infants and children less than 5 years due to food sensitivity (milk, egg, soy, and wheat proteins) followed by respiratory disease (rhinitis and asthma) in older children and adults due to sensitivity to inhalant allergens (dust mite, mold, and pollen inhalants).
PROGESTERONE
Sources of progesterone are the adrenal glands, corpus luteum, and placenta.
Adrenal Glands:
Progesterone synthesized in the adrenal glands is converted to other corticosteroids and androgens and, thus, is not a major contributor to circulating serum levels unless there is a progesterone-producing tumor present.
Corpus Luteum:
After ovulation, there is a significant rise in serum levels as the corpus luteum begins to produce progesterone in increasing amounts. This causes changes in the uterus, preparing it for implantation of a fertilized egg. If implantation occurs, the trophoblast begins to secrete human chorionic gonadotropin, which maintains the corpus luteum and its secretion of progesterone. If there is no implantation, the corpus luteum degenerates and circulating progesterone levels decrease rapidly, reaching follicular phase levels about 4 days before the next menstrual period.
Placenta:
By the end of the first trimester, the placenta becomes the primary secretor of progesterone.
PROLACTIN
Prolactin is secreted by the anterior pituitary gland and controlled by the hypothalamus. The major chemical controlling prolactin secretion is dopamine, which inhibits prolactin secretion from the pituitary. Prolactin is released from the pituitary in response to thyrotropin-releasing hormone and other factors.
Prolactin is the principal hormone that controls the initiation and maintenance of lactation. In normal individuals, prolactin concentrations increase in response to physiologic stimuli such as sleep, stress, exercise, sexual intercourse, and hypoglycemia, and concentrations are also elevated during pregnancy, lactation, postpartum, and in a newborn infant.
sFLT-1
sFlt-1 (sVEGFR-1) is an antiangiogenic factor expressed as an alternatively spliced variant of VEGFR-1 that lacks both the transmembrane and cytoplasmic domains. sFlt-1 binds VEGF and PlGF and blocks their angiogenic effects on VEGFR. sFlt-1 may also form a heterodimer with the surface membrane VEGFR-1 and inhibit its postreceptor signaling actions.
SHBG
Sex hormone-binding globulin (SHBG), a 95 KDa homodimer, is the blood transport protein for testosterone and estradiol. SHBG is mainly produced in the liver and has a half-life of approximately seven days. SHBG binds reversibly to sex steroids. SHBG has a relatively high binding affinity to dihydrotestosterone (DHT), medium affinity to testosterone and estradiol, and exhibits a low affinity to estrone, dehydroepiandrosterone (DHEA), androstenedione, and estriol. Albumin, which exists at physiologically higher concentrations than SHBG, also binds to sex steroids although with a much lower binding affinity (eg, about 100 times lower for testosterone).
Decreased SHBG serum concentrations are associated with conditions in which elevated androgen concentrations are present or the effect of androgen on its target organs is excessive. Because of the high binding affinity of SHBG to DHT, as compared to estradiol, SHBG has profound effects on the balance between bioavailable androgens and estrogens. Increased SHBG concentrations may be associated with symptoms and signs of hypogonadism in men, while decreased concentrations can result in androgenization in women. SHBG is also regulated by insulin, and a low SHBG concentration often indicates insulin resistance and, consequently, may be a predictor of type 2 diabetes.
Endogenous or exogenous thyroid hormones or estrogens increase SHBG concentrations. In men, there is also an age-related gradual rise, possibly secondary to the mild age-related fall in testosterone production. This process can result in bioavailable testosterone concentrations that are much lower than would be expected based on total testosterone measurements alone.
TESTOSTERONE II
Testosterone is the major androgenic hormone. It is responsible for the development of the male external genitalia and secondary sexual characteristics. In females, its main role is as an estrogen precursor. In both genders, it also exerts anabolic effects and influences behavior.
In men, testosterone is secreted by the testicular Leydig cells and, to a minor extent, by the adrenal cortex. In premenopausal women, the ovaries are the main source of testosterone with minor contributions by the adrenals and peripheral tissues. After menopause, ovarian testosterone production is significantly diminished. Testosterone production in testes and ovaries is regulated via pituitary-gonadal feedback involving luteinizing hormone (LH) and, to a lesser degree, inhibins and activins.
Most circulating testosterone is bound to sex hormone-binding globulin (SHBG), which, in men, also is called testosterone-binding globulin. A lesser fraction is albumin bound and a small proportion exists as free hormone. Historically, only free testosterone was thought to be the biologically active component. However, testosterone is weakly bound to serum albumin and dissociates freely in the capillary bed, thereby becoming readily available for tissue uptake. All non-SHBG-bound testosterone is therefore considered bioavailable.
UNCONJUGATED ESTRIOL
Estrogens are involved in development and maintenance of the female phenotype, germ cell maturation, and pregnancy. There are 3 major biologically active estrogens in humans: estrone (E1), estradiol (E2), and estriol (E3). Like all members of the steroid hormone family, they diffuse into cells and bind to specific nuclear receptors, which in turn alter gene transcription in a tissue specific manner. E2 is the most potent natural human estrogen, closely followed by E1, while E3 possess only 20% of the E2 affinity for the estrogen receptor. In men and nonpregnant women, E1 and E2 are formed from the androgenic steroids androstenedione and testosterone, respectively. E3 is derived largely through conversion of E2, and to a lesser degree from 16a-metabolites of E1. E2 and E1 can also be converted into each other, and both can be inactivated via hydroxylation and conjugation.
During pregnancy E3 becomes the dominant estrogen. The fetal adrenal gland secretes dehydroepiandrosterone-sulfate (DHEAS), which is converted to E3 in the placenta and diffuses into the maternal circulation. The half-life of unconjugated E3 (uE3) in the maternal blood system is 20 to 30 minutes since the maternal liver quickly conjugates E3 to make it more water soluble for urinary excretion. E3 levels increase throughout the course of pregnancy, peaking at term.
Decreased second trimester uE3 has been shown to be a marker for Down and trisomy-18 syndromes. uE3 is a part of multiple marker prenatal biochemical screening, together with alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), and inhibin-A measurements. Low levels of uE3 also have been associated with pregnancy loss, Smith-Lemli-Opitz syndrome (defect in cholesterol biosynthesis), X-linked ichthyosis and contiguous gene syndrome (placental sulfatase deficiency disorders), aromatase deficiency, and primary or secondary fetal adrenal insufficiency.
C-PEPTIDE
C-peptide (connecting peptide), a 31-amino-acid polypeptide, represents the midportion of the proinsulin molecule. Proinsulin resembles a hairpin structure, with an N-terminal and C-terminal, which correspond to the A and B chains of the mature insulin molecule, oriented parallel to each other and linked by disulfide bonds. The looped portion of the hairpin between the A and B chains is called C-peptide. During insulin secretion, C-peptide is enzymatically cleaved off and cosecreted in equimolar proportion with mature insulin molecules.
Following secretion, insulin and C-peptide enter the portal circulation and are routed through the liver where at least 50% of the insulin binds to receptors, initiates specific hepatic actions (stimulation of hepatic glucose uptake and suppression of glycogenolysis, gluconeogenesis, and ketogenesis), and is subsequently degraded. Most of the insulin molecules that pass through the liver into the main circulation bind to peripheral insulin receptors, promoting glucose uptake, while the remaining molecules undergo renal elimination. Unlike insulin, C-peptide is subject to neither hepatic nor significant peripheral degradation but is mainly removed by the kidneys. As a result, C-peptide has a longer half-life than insulin (30-35 minutes versus 5-10 minutes), and the molar ratio of circulating insulin to circulating C-peptide is generally below 1, despite equimolar secretion. Until recently, C-peptide was thought to have no physiological function, but it now appears that there may be specific C-peptide cell-surface receptors (most likely belonging to the super-family of G-protein coupled receptors), which influence endothelial responsiveness and skeletal and renal blood flow.
FRUCTOSAMINE
Fructosamine is a general term, which applies to any glycated protein. It is formed by the nonenzymatic reaction of glucose with the a- and e-amino groups of proteins to form intermediate compounds called aldimines. These aldimines may dissociate or undergo an Amadori rearrangement to form stable ketoamines called fructosamines. This nonenzymatic glycation of specific proteins in vivo is proportional to the prevailing glucose concentration during the lifetime of the protein. Therefore, glycated protein measurement in the diabetic patient is felt to be a better monitor of long-term glycemic control than individual or sporadic glucose determinations. The best known of these proteins is glycated hemoglobin which is often measured as hemoglobin A1c, and reflects glycemic control over the past 6 to 8 weeks. In recognition of the need for a measurement that reflects intermediate-term glycemic control and was easily automated, a nonspecific test, termed fructosamine, was developed. Since albumin is the most abundant serum protein, it accounts for 80% of the glycated serum proteins, and thus, a high proportion of the fructosamine. Although a large portion of the color generated in the reaction is contributed by glycated albumin, the method will measure all proteins, each with a different half-life and different levels of glycation.
GLUCOSE
The most common disease related to carbohydrate metabolism is diabetes mellitus, which is characterized by insufficient blood levels of active insulin. Symptoms include polyuria, abnormally elevated blood and urine glucose values, excessive thirst, constant hunger, sudden weight loss, and possibly elevated blood and urine ketones. Complications from diabetes are the third leading cause of death in the United States. There are approximately 16 million diabetics in the United States, and that number is growing. It is estimated that at least 5 million of these people have not been diagnosed. The prevalence in the population age 65 and older is 18.4%, representing 6.3 million cases. The cost of diabetes to the US economy exceeds $92 billion annually.
Overproduction or excess administration of insulin causes a decrease in blood glucose to levels below normal. In severe cases, the resulting extreme hypoglycemia is followed by muscular spasm and loss of consciousness, known as insulin shock.
HbA1c
Hemoglobin A1c (HbA1c) is a result of the nonenzymatic attachment of a hexose molecule to the N-terminal amino acid of the hemoglobin molecule. The attachment of the hexose molecule occurs continually over the entire life span of the erythrocyte and is dependent on blood glucose concentration and the duration of exposure of the erythrocyte to blood glucose. Therefore, the HbA1c level reflects the mean glucose concentration over the previous period (approximately 8-12 weeks, depending on the individual) and provides a much better indication of long-term glycemic control than blood and urinary glucose determinations. Diabetic patients with very high blood concentrations of glucose have from 2 to 3 times more HbA1c than normal individuals.
INSULIN
Hemoglobin A1c (HbA1c) is a result of the nonenzymatic attachment of a hexose molecule to the N-terminal amino acid of the hemoglobin molecule. The attachment of the hexose molecule occurs continually over the entire life span of the erythrocyte and is dependent on blood glucose concentration and the duration of exposure of the erythrocyte to blood glucose. Therefore, the HbA1c level reflects the mean glucose concentration over the previous period (approximately 8-12 weeks, depending on the individual) and provides a much better indication of long-term glycemic control than blood and urinary glucose determinations. Diabetic patients with very high blood concentrations of glucose have from 2 to 3 times more HbA1c than normal individuals.
ANTI-INSULIN
Insulin antibodies may be found in nondiabetic individuals complaining of hypoglycemic attacks. In this setting their presence can be an indicator of "factitious hypoglycemia" due to the surreptitious injection of insulin, rather than to a clinical problem (eg, insulinoma). However, insulin autoantibodies in nondiabetic subjects can occasionally develop without exposure to exogenous insulin and may rarely become a cause of episodic hypoglycemia. Anti-idiotypic autoantibodies against insulin autoantibodies have been demonstrated in some cases. Interaction of these antibodies with insulin autoantibodies could displace bound insulin from the insulin autoantibodies, resulting in hypoglycemia.
In addition to IgG and IgM insulin autoantibodies, IgE antibodies (identified by the fluorescence enzyme immunoassay) may occur. IgE insulin autoantibodies result in immediate hypersensitivity reactions, such as urticaria, but do not lead to insulin resistance or hypoglycemia as can be seen with the IgG antibodies. This test only determines the presence of IgG and IgM antibodies, not IgE antibodies.
AFP
Alpha-fetoprotein (AFP) is a glycoprotein that is produced in early fetal life by the liver and by a variety of tumors including hepatocellular carcinoma, hepatoblastoma, and nonseminomatous germ cell tumors of the ovary and testis (eg, yolk sac and embryonal carcinoma). Most studies report elevated AFP concentrations in approximately 70% of patients with hepatocellular carcinoma. Elevated AFP concentrations are found in 50% to 70% of patients with nonseminomatous testicular tumors.(1)
AFP is elevated during pregnancy. Persistence of AFP in the mother following birth is a rare hereditary condition.(2) Neonates have markedly elevated AFP levels (>100,000 ng/mL) that rapidly fall to below 100 ng/mL by 150 days and gradually return to normal over their first year.(2)
Concentrations of AFP above the reference range also have been found in the serum of patients with benign liver disease (eg, viral hepatitis, cirrhosis), gastrointestinal tract tumors, and along with carcinoembryonic antigen, in ataxia telangiectasia.
The biological half-life of AFP is approximately 5 days.
BR 27.79
Carcinoma of the breast is the most prevalent form of cancer in women. These tumors often produce mucinous antigens, which are large-molecular-weight glycoproteins with O-linked oligosaccharide chains.
Monoclonal antibodies directed against these antigens have been developed, and several immunoassays are available to quantitate the levels of tumor-associated mucinous antigens in serum. The antibodies recognize epitopes of a breast cancer-associated antigen encoded by the human mucin 1 (MUC-1) gene, which is known by several names including MAM6, milk mucin antigen, cancer antigen (CA) 27.29, and CA 15-3.
While CA 27.29 is expressed at the apical surface of normal epithelial cells, it is present throughout malignant epithelial cells of the breast, lung, ovary, pancreas, and other sites. The cancer-associated form of the antigen is less extensively glycosylated than the normal form and more specific for tumor cells.
CA 125II
Cancer antigen 125 (CA 125) is a glycoprotein antigen normally expressed in tissues derived from coelomic epithelia (ovary, fallopian tube, peritoneum, pleura, pericardium, colon, kidney, stomach).
Serum CA 125 is elevated in approximately 80% of women with advanced epithelial ovarian cancer, but assay sensitivity is suboptimal in early disease stages. The average reported sensitivities are 50% for stage I and 90% for stage II or greater.
Elevated serum CA 125 levels have been reported in individuals with a variety of nonovarian malignancies including cervical, liver, pancreatic, lung, colon, stomach, biliary tract, uterine, fallopian tube, breast, and endometrial carcinomas.
Elevated serum CA 125 levels have been reported in individuals with a variety of benign conditions including: cirrhosis, hepatitis, endometriosis, first trimester pregnancy, ovarian cysts, and pelvic inflammatory disease. Elevated levels during the menstrual cycle also have been reported.
CA 15-3
Carcinoma of the breast is the most prevalent form of cancer in women. These tumors often produce mucinous antigens, which are large molecular weight glycoproteins with O-linked oligosaccharide chains. Tumor-associated antigens encoded by the human MUC-1 gene are known by several names, including MAM6, milk mucin antigen, cancer antigen (CA) 27.29, and CA 15-3.
CA 15-3 assay values are not elevated in most normal individuals and are frequently elevated in sera from breast cancer patients.
Nonmammary malignancies in which elevated CA 15-3 assay values have been reported include: lung, colon, pancreas, primary liver, ovary, cervix, and endometrium.
CA 19-9
Carbohydrate antigen 19-9 (CA 19-9) is a modified Lewis(a) blood group antigen. CA 19-9 may be elevated in patients with gastrointestinal malignancies such as cholangiocarcinoma, pancreatic cancer, or colon cancer.
Benign conditions such as cirrhosis, cholestasis, and pancreatitis also result in elevated serum CA 19-9 concentrations but in these cases values usually are below 1000 U/mL.
Individuals that are Lewis negative (5%-7% of the population) do not express CA 19-9 due to the lack of the enzyme fucosyltransferase needed for CA 19-9 production. In these individuals, a low or undetectable serum CA 19-9 concentration is not informative regarding cancer recurrence.
CALCITONIN
Calcitonin is a polypeptide hormone secreted by the parafollicular cells (also referred to as calcitonin cells or C cells) of the thyroid gland. The main action of calcitonin is the inhibition of bone resorption by regulating the number and activity of osteoclasts. Calcitonin is secreted in direct response to serum hypercalcemia and may prevent large oscillations in serum calcium levels and excessive loss of body calcium. However, in comparison to parathyroid hormone and 1,25-dihydroxyvitamin D, the role of calcitonin in the regulation of serum calcium in humans is minor. Measurements of serum calcitonin levels are, therefore, not useful in the diagnosis of disorders of calcium homeostasis.
Malignant tumors arising from thyroid C cells (medullary thyroid carcinoma: MTC) usually produce elevated levels of calcitonin. MTC is an uncommon malignant thyroid tumor, comprising less than 5% of all thyroid malignancies. Approximately 25% of these are familial cases, usually appearing as a component of multiple endocrine neoplasia type II (MENII, Sipple syndrome). MTC may also occur in families without other associated endocrine dysfunction, with similar autosomal dominant transmission as MENII, which is then called familial medullary thyroid carcinoma (FMTC). Variants in the RET proto-oncogene are associated with MENII and FMTC.
Serum calcitonin concentrations are high in infants, decline rapidly, and are relatively stable from childhood through adult life. In general, calcitonin serum concentrations are higher in men than in women due to the larger C-cell mass in men. Serum calcitonin concentrations may be increased in patients with chronic renal failure, and other conditions such as hyperparathyroidism, leukemic and myeloproliferative disorders, Zollinger-Ellison syndrome, autoimmune thyroiditis, small cell and large cell lung cancers, breast and prostate cancer, mastocytosis, and various neuroendocrine tumors, in particular, islet cell tumors.
CEA
Carcinoembryonic antigen (CEA) is a glycoprotein normally found in embryonic entodermal epithelium.
Increased levels may be found in patients with primary colorectal cancer or other malignancies including medullary thyroid carcinoma and breast, gastrointestinal tract, liver, lung, ovarian, pancreatic, and prostatic cancers.
Serial monitoring of CEA should begin prior to therapy to verify post therapy decrease in concentration and to establish a baseline for evaluating possible recurrence. Levels generally return to normal within 1 to 4 months after removal of cancerous tissue.
COMPLEXED PSA
Prostate specific antigen (PSA) is a protein produced primarily by cells in the prostate, a small gland in males that encircles the urethra and produces a fluid that makes up part of semen. Most of the PSA that the prostate produces is released into this fluid, but small amounts of it are also released into the blood. PSA exists in two main forms in the blood: complexed (cPSA, bound to other proteins) and free (fPSA, not bound). The most frequently used PSA test is the total PSA, which measures the sum of cPSA and fPSA in the blood.
The PSA test may be used as a tumor marker to screen for and to monitor prostate cancer. The goal of screening is to detect prostate cancer while it is still confined to the prostate. However, most experts agree that screening should be done on asymptomatic men only after thorough discussions with their healthcare practitioners on the benefits and risks and after informed decisions are made to undergo screening. Elevated blood levels of PSA are associated with prostate cancer, but they may also be seen with inflammation of the prostate (prostatitis) and benign prostatic hyperplasia (BPH). PSA levels tend to increase in all men as they age, and men of African American heritage may have levels that are higher than other men, even at earlier ages
FREE PSA
Prostate specific antigen (PSA) is a protein produced primarily by cells in the prostate, a small gland in males that encircles the urethra and produces a fluid that makes up part of semen. Most of the PSA that the prostate produces is released into this fluid, but small amounts of it are also released into the blood. PSA exists in two main forms in the blood: complexed (cPSA, bound to other proteins) and free (fPSA, not bound). The most frequently used PSA test is the total PSA, which measures the sum of cPSA and fPSA in the blood.
The PSA test may be used as a tumor marker to screen for and to monitor prostate cancer. The goal of screening is to detect prostate cancer while it is still confined to the prostate. However, most experts agree that screening should be done on asymptomatic men only after thorough discussions with their healthcare practitioners on the benefits and risks and after informed decisions are made to undergo screening. Elevated blood levels of PSA are associated with prostate cancer, but they may also be seen with inflammation of the prostate (prostatitis) and benign prostatic hyperplasia (BPH). PSA levels tend to increase in all men as they age, and men of African American heritage may have levels that are higher than other men, even at earlier ages.
PSA
Prostate-specific antigen (PSA) is a glycoprotein that is produced by the prostate gland, the lining of the urethra, and the bulbourethral gland. Normally, very little PSA is secreted in the blood. Increases in glandular size and tissue damage caused by benign prostatic hypertrophy, prostatitis, or prostate cancer may increase circulating PSA levels.
In patients with previously diagnosed prostate cancer, PSA testing is advocated as an early indicator of tumor recurrence and as an indicator of response to therapy. The role of PSA in early detection of prostate cancer is controversial. The American Cancer Society recommends annual examination with digital rectal examination and serum PSA beginning at age 50, and also for those men with a life expectancy of at least 10 years after detection of prostate cancer. For men in high-risk groups, such as African Americans or men with a first-degree relative diagnosed at a younger age, testing should begin at a younger age. It is generally recommended that information be provided to patients about the benefits and limitations of testing and treatment so they can make informed decisions.
Source: https://www.mayocliniclabs.com
B2 MICROGLOBULIN
Beta-2-microglobulin (beta-2-M) is a small membrane protein (11,800 Dalton) associated with the heavy chains of class I major histocompatibility complex proteins and is, therefore, on the surface of all nucleated cells. The small size allows beta-2-M to pass through the glomerular membrane, but it is almost completely reabsorbed in the proximal tubules.
Serum beta-2-M levels are elevated in diseases associated with increased cell turnover. Levels are also elevated in several benign conditions such as chronic inflammation, liver disease, renal dysfunction, some acute viral infections, and a number of malignancies, especially hematologic malignancies associated with the B-lymphocyte lineage.
In multiple myeloma, beta-2-M is a powerful prognostic factor and values <4 mcg/mL are considered a good prognostic factor.
In renal tubular disease, serum levels are low and urine levels are high. Although urine beta-2-M has been used to assess tubular dysfunction, it is not stable in urine below pH 5.5.
HER2/NEU , SERUM
The HER-2/neu oncogene (erbB-2) encodes a protein with a molecular weight of 185,000 daltons (p185). This oncogene belongs to a family of cell surface receptors with intracellular tyrosine kinase activity, and is structurally related to the Epidermal Growth Factor Receptor (erbB-1). The HER-2/neu protein is composed of a cytoplasmic domain, a transmembrane domain, and an extracellular domain (ECD).1–3 Since the mid-1980s the HER-2/neu oncogene and its protein product have been reported to play a role in the development and metastasis of breast cancer.4,5 The shed ECD has been shown to be a glycoprotein, usually referred to as p105, with a molecular weight ranging from 97 kilodaltons to 115 kilodaltons.6–8 Numerous reports have shown that ECD is shed in the blood of normal individuals and is elevated in a subset of women with metastatic breast cancer.9–12 In addition, there are reports that HER-2/neu protein is overexpressed in a number of other tumor types of epithelial origin, including lung, hepatocellular, pancreatic, colon, stomach, ovarian, cervical, and bladder cancer.
ACETAMINOPHEN
Acetaminophen is an analgesic found in many “over-the-counter” pain remedies. It is rapidly and completely absorbed from the gastrointestinal tract. After oral administration, peak plasma concentrations are reached in less than an hour. Approximately 90% of a therapeutic dose is eliminated by conjugation with glucoronic acid (and to a slight extent, sulfuric acid) in the liver. Another 3 – 5% is catabolized by the P-450 mixed function oxidase enzyme system to the acid and cysteine conjugates. All of these metabolites are excreted in the urine. Only a slight amount of the drug is excreted unchanged. Intermediate metabolites of uncertain structure formed during the biotransformation in the liver are believed to be responsible for the hepatotoxicity. After a therapeutic dose of acetaminophen, the biologic half-life in normal adults is 2 – 3 hours. Metabolism is more rapid in children (except newborns). Because the hepatic conjugation is the rate-limiting step in the catabolic pathway, the half-life is prolonged in patients with liver disease, alcoholics, or in the presence of other drugs which compete for the hepatic conjugation mechanism. Acetaminophen does not have anti-inflammatory activity and it does not affect blood clotting (hemostasis). It is preferred over aspirin when the hemostatic side effects of aspirin must be avoided. Severe liver damage in adults is generally associated with ingestion of 15 grams or more. Since the drug is catabolized in the liver, hepatoxicity will result in elevated plasma drug levels and prolonged half-life. The availability of a rapid accurate plasma acetaminophen assay is of extreme importance in cases of suspected intoxication because effective antidotes are available. Therapy with N-acetylcysteine (NAC) must be started within eight hours after ingestion to prevent hepatic injury as signified by elevations in AST and ALT.1,2
AMPHETAMINS
Amphetamines are central nervous system stimulants that produce wakefulness, alertness, increased energy, reduced hunger, and an overall feeling of well-being. The term “amphetamine” includes many drugs, but d-amphetamine, d-methamphetamine (the N-methyl derivative of amphetamine), and d,l-amphetamine are the most common1 . Amphetamines can be taken orally, intravenously, by smoking, or by snorting1 . Amphetamines are readily absorbed from the gastrointestinal tract and are then either deactivated by the liver or excreted unchanged in the urine. The relative importance of these elimination modes depends on urinary pH. Amphetamine is metabolized to deaminated (hippuric and benzoic acids) and hydroxylated metabolites. Methamphetamine is partially metabolized to amphetamine, its major active metabolite.1 Amphetamines appear in the urine within three hours after any type of administration,1 and can be detected by this Emit® assay for as long as 24 – 48 hours after the last dose.1
BARBITURATES
Barbiturates, a class of nervous system depressants, are usually taken orally, but are sometimes injected intravenously or intramuscularly. They are absorbed rapidly; 30 – 40% is bound to plasma protein, and the rest is distributed to muscle, fat, and to the liver (where they are ultimately inactivated).1 They are classified based on their duration of action, ranging from very short acting (approximately 15 minutes) to long acting (a day or more). Some of the most commonly abused barbiturates are the short-acting ones, including pentobarbital and secobarbital. An example of a long-acting barbiturate is phenobarbital. The ratio of unchanged drug to metabolites varies depending upon duration of action. Short-acting barbiturates will generally be excreted in urine as metabolites, while the long-acting barbiturates will primarily appear unchanged.1
BENZODIAZEPINE
Benzodiazepines are sedative-hypnotic drugs that are structurally similar and include widely used drugs such as chlordiazepoxide, diazepam, and oxazepam. The different benzodiazepines are absorbed at different rates, and the timing of their psychoactive effects varies with the absorption rate. Benzodiazepines are usually taken orally and are metabolized in the liver. Some benzodiazepine metabolites are pharmacologically active.1 Benzodiazepines potentiate the effect of other central nervous system depressants, such as ethyl alcohol.1
CANNABINOOID (THC)
Marijuana is a mixture of dried leaves and flowering tops of the plant Cannabis sativa L. The agents that produce the hallucinogenic and other biological effects of marijuana are called cannabinoids. The cannabinoid ∆9 -tetrahydrocannabinol (∆9 -THC) is the principal psychoactive ingredient in marijuana and hashish. The compound ∆9 -THC is quickly and effectively absorbed by inhalation or from the gastrointestinal tract,1 and is almost completely metabolized by liver enzymes.1 Peak plasma levels of ∆9 -THC occur within 10 minutes of inhalation and approximately 1 hour after ingestion.1 Approximately 30% of a dose of THC is excreted as urinary metabolites within 72 hours after exposure.1 Concentration depends on the total amount of THC absorbed, frequency of abuse, rate of release from fatty tissue, and time of specimen collection with respect to use. In chronic users, THC may accumulate in fatty tissue faster than it can be eliminated. This accumulation leads to longer detection times in urinalysis for chronic users than for occasional users.1
COCAINE METABOLITE
Cocaine is a central nervous system stimulant that is extracted from the coca plant. As a drug of abuse, it is self administered in a variety of ways, including inhalation and intravenous injection. Cocaine base can be smoked in a form that is commonly known as “crack.” Cocaine is rapidly absorbed, especially when smoked. While all forms are potentially addicting, “crack” is especially likely to lead to dependence because of its more rapid and heightened effect on the abuser.1 Excretion rate patterns vary with the mode of administration and from individual to individual. Cocaine is almost completely metabolized, primarily in the liver, with only about one percent excreted in the urine unchanged. Most cocaine is eliminated as benzoylecgonine, the major metabolite of cocaine. Cocaine is also excreted in relatively lesser amounts as ecgonine methyl ester and ecgonine. Cocaine metabolites may be detected in urine for up to a couple of days after cocaine is used. Benzoylecgonine can be detected in urine within four hours after cocaine inhalation and remain detectable in concentrations greater than 1000 ng/mL for as long as 48 hours.1
ECSTACY
“Ecstasy” is the popular street name used to refer to methylenedioxymethamphetamine (MDMA). Ecstasy and related drugs, methylenedioxyamphetamine (MDA) and methylenedioxyethylamphetamine (MDEA), are amphetamine derivatives. The tablets, as sold illicitly in Europe and North America, may also include amphetamine and methamphetamine in the preparation.1 Ecstasy drugs are listed by the U.S. Drug Enforcement Administration as Schedule I designating no acceptable medical application with great abuse potential. These compounds are central nervous system stimulants that produce an initial feeling of euphoria and also a feeling of increased well-being, self esteem, with heightened mental and physical capacity.1 Adverse effects include confusion, ataxia, restlessness, poor concentration, and psychoses. Long-term consequences of its abuse include changes in mood, sleep disturbances, anxiety, and impairment in cognition and memory.3 MDMA is readily absorbed from the intestinal tract. Peak plasma concentrations occur approximately 2 hours after oral dose and are generally low, since MDMA passes readily into tissues. MDMA is metabolized in the liver and the excretion of the drug occurs with over 95% of the drug cleared in about 2 days.1 Approximately 65% of the drug is excreted unchanged, with 10 – 15% of the dose excreted as methylenedioxyamphetamine (MDA) and a similar small amount converted to amphetamine and methamphetamine.1,4 Methods historically used for detecting MDMA in biological fluids include high-performance liquid chromatography, gas-liquid chromatography, and enzyme immunoassay.1 While confirmation techniques other than GC/MS may be adequate for some drugs of abuse, GC/MS is generally accepted as a vigorous confirmation technique for all drugs, since it provides the best level of confidence in the result.
EDDP (METHADONE METABOLITE)
Methadone is a synthetic opioid that suppresses the craving for heroin or other morphine-like drugs while blocking their intense euphoric effects. Methadone is commonly used in treatment facilities to detoxify and maintain heroin addicts. Methadone compliance is essential and can be effectively monitored by urine screening for methadone and its metabolites. When methadone is administered, it is quickly metabolized by the liver into normethadone by N-demethylation. Normethadone readily dehydrates to form EDDP (2-ethylidine-1,5- dimethyl-3,3-diphenylpyrrolidine), the primary metabolite of methadone. Further demethylation of EDDP forms 2-ethyl-5-methyl-3,3-diphenyl-1-pyrroline (EMDP), the secondary metabolite of methadone, which is present in lower concentrations. 11110145_EN Rev. 02, 2019-07 1 / 14 Various immunoassay techniques are currently available for methadone compliance monitoring. However, these tests measure the parent drug (methadone) only and are subject to “false positives” from patients who add a portion of their methadone directly into the urine sample. As a result, confirmation of the presence of EDDP by thin layer chromatography (TLC) or gas chromatography (GC) is often required. Demonstration of the presence of EDDP in urine with an immunoassay makes widespread testing for compliance possible and negates the benefit of sample tampering with methadone. The assay measures methadone metabolite in human urine using a homogenous competitive enzyme immunoassay.
ETHYL ALCOHOL
Ethyl alcohol is the most widespread and heavily consumed drug in human experience. It produces a loss of equilibrium, a sense of euphoria and loss of inhibition. While some ethanol is absorbed through the stomach, the primary site of absorption is the small intestine. The presence of food in the stomach results in a smaller peak concentration being reached. Ethanol is distributed uniformly throughout the body water and readily crosses the blood-brain barrier. In addition, ethanol crosses the placenta of pregnant women, a phenomenon that may cause a potentially serious disorder known as fetal alcohol syndrome.1 Ethyl alcohol is metabolized to acetaldehyde and then to acetic acid by liver enzymes. About 95% of a dose undergoes metabolism by the liver.2
METHADONE
Methadone is a synthetic narcotic/analgesic drug that is administered orally or intravenously. Medically assisted withdrawal from opioids is usually accomplished using methadone. Methadone is frequently used in maintenance programs as a substitute for heroin or other abused opioids, while allowing the subject to successfully participate in drug rehabilitation. Patients are able to function well on methadone and perform complex tasks competently.1 Methadone is metabolized in the liver. The kidneys become a major route of methadone excretion at doses exceeding 50 mg/dL. Urine levels in methadone maintenance patients range from 1 to 5 µg/mL 24 hours after methadone dose.1
METHAQUALONE
Methaqualone is a sedative-hypnotic drug that is usually taken orally. Methaqualone is metabolized extensively in the liver and excreted in the urine in the form of six major metabolites.2 The drug and its metabolites collect in fat with a large volume of distribution (2.4–6.4 L/kg). They are usually eliminated slowly over several days, but may accumulate during multiple dosing.2,3 Methaqualone and its metabolites have been detected in urine for up to two weeks in concentrations of 0.5–1.0 µg/mL after a single 300 mg dose.4
OPIATE
Opiates are a class of compounds that includes morphine, codeine, and heroin. Morphine and codeine are naturally occurring alkaloids that are found in opium, a substance exuded from the unripe seed pod of the opium poppy Papaver somniferum. Heroin is a semisynthetic derivative of morphine.1 Morphine is a potent analgesic. Codeine is used in analgesic preparations and as a cough suppressant. Heroin is an even more potent analgesic than morphine. Both morphine and codeine are legitimate drugs. Heroin is a drug of abuse that may be snorted, smoked, or dissolved and injected subcutaneously or intravenously. Opiates are absorbed rapidly. Heroin is converted almost immediately to morphine, which is excreted in urine both unchanged and as a glucuronidated metabolite. Excretion takes place over a period of a couple of days. Codeine is excreted in urine as a glucuronidated conjugate, as free and conjugated norcodeine, and as morphine. The presence of opiates in the urine indicates the use of heroin, morphine, and/or codeine. 6-Acetylmorphine (6-AM) is a metabolite of heroin; its presence is positive proof of heroin use. 6-AM has a very short half-life (ie, it is detectable for only a few hours after heroin use). Current literature shows that 10 ng/mL is the lowest testing level by GC/MS that can reasonably be used to consistently and accurately identify and quantitate the presence of 6-AM.1
OXYCODONE
Oxycodone is a semi-synthetic opioid analgesic prescribed for the relief of moderate to severe pain. Oxycodone structurally resembles codeine and morphine, with similar analgesic properties and potential for addiction and abuse. Oxycodone is a DEA Schedule II drug. The drug oxycodone is prescribed in controlled-release form (OxyContin), or in combination with acetaminophen (Percocet) or with aspirin (Percodan). Oxycodone is metabolized in the human liver primarily by N- and O-methylation to oxymorphone, noroxycodone, and noroxymorphone.3 Oxymorphone is a potent, pharmacologically active analgesic that is further metabolized in the liver to oxymorphone glucuronides.3 Noroxycodone and noroxymorphone are relatively inactive.3 The parent compound and metabolites are excreted in urine. The Atellica CH OXY assay detects oxycodone and oxymorphone in human urine. The assay demonstrates no to minimum cross-reactivity with other structurally-related opiates and opioid compounds. While confirmation techniques other than GC/MS or LC/MS may be adequate for some drugs of abuse, GC/MS or LC/MS is generally accepted as a vigorous confirmation technique for all drugs, since it provides the best level of confidence in the result.
PHENCYCLIDINE
Phencyclidine, also known as PCP and “angel dust”, is a synthetic drug that was originally developed for its anesthetic properties but is now a drug of abuse used solely for its potent hallucinogenic effects. It may be self-administered in a variety of ways, including ingestion, inhalation, and intravenous injection. Phencyclidine is absorbed well and quickly, and concentrates in the brain and fatty tissues1 . Excretion patterns vary widely, ranging from several hours to a couple of weeks. Phencyclidine is excreted in the urine unchanged, as conjugated metabolites, and primarily as unidentified compounds.
PROPOXYPHENE
Propoxyphene and propoxyphene napsylate, a propoxyphene salt, are mildly effective narcotic analgesics used to treat mild to moderate pain. Propoxyphene is structurally related to methadone and produces central nervous system effects similar to those of morphine-like opioids. When given orally, propoxyphene is one-half to two-thirds as potent as codeine and has a similar incidence of side effects, which include nausea, anorexia, constipation, abdominal pain, and drowsiness. A synergistic effect is produced when propoxyphene is given in combination with aspirin.2 Propoxyphene and propoxyphene napsylate may be toxic and even fatal at levels that exceed the recommended therapeutic dosages, particularly because they are metabolized quickly. In addition to respiratory depression, toxic doses may produce convulsions, delusions, hallucinations, confusion, cardiotoxicity, and pulmonary edema.2 The Atellica CH Ppx assay uses a cutoff of 300 ng/mL propoxyphene. The assay detects propoxyphene and propoxyphene salts, such as propoxyphene napsylate, in human urine. It also detects norpropoxyphene (N-desmethyldextropropoxyphene), the major urinary metabolite of propoxyphene. Positive results for specimens containing other compounds structurally unrelated to propoxyphene have not been observed. Methods historically used for detecting propoxyphene in biological fluids include ultraviolet spectrophotometry, gas chromatography, and enzyme immunoassay.3 While confirmation techniques other than GC/MS may be adequate for some drugs of abuse, GC/MS is generally accepted as a rigorous confirmation technique for all drugs, since it provides the best level of confidence in the result.1
SALICYLATE
Salicylates (aspirin, acetylsalicylic acid) have analgesic, antipyretic, and anti-inflammatory properties and have been used for centuries to relieve pain. Salicylate overdose may cause intoxication. Measurement of salicylate concentration is important for assessment of the severity of intoxication.1
TRAMADOL
Tramadol is used to relieve moderate to moderately severe pain, including pain after surgery. The extended-release capsules or tablets are used for chronic ongoing pain.
Tramadol belongs to the group of medicines called opioid analgesics. It acts in the central nervous system (CNS) to relieve pain.
When tramadol is used for a long time, it may become habit-forming, causing mental or physical dependence. However, people who have continuing pain should not let the fear of dependence keep them from using narcotics to relieve their pain. Mental dependence (addiction) is not likely to occur when narcotics are used for this purpose. Physical dependence may lead to withdrawal side effects if treatment is stopped suddenly. However, severe withdrawal side effects can usually be prevented by gradually reducing the dose over a period of time before treatment is stopped completely
ACTIVE - B12
Vitamin B12 (cobalamin) in serum is bound to two proteins: transcobalamin and haptocorrin. The transcobalamin-vitamin B12 complex is called holotranscobalamin (holoTC). HoloTC contains the biologically available cobalamin as only holoTC promotes the uptake of cobalamin by all cells via specific receptors. In comparison, approximately 80% of the circulating cobalamin, that is carried by haptocorrin, is considered metabolically inert because no cellular receptors exist, with the exception of receptors found in the liver.
Genetic absence of haptocorrin is rare and not considered a serious condition. Genetic absence or abnormalities of transcobalamin, however, manifest as typical hematological, neurological, and metabolic pathologies of cobalamin deficiency, which require aggressive treatment even if a serum analysis results in normal cobalamin concentrations.
EPO
Erythropoietin (EPO) is a glycoprotein hormone consisting of 165 amino acids, with 4 complex carbohydrate chains attached to the peptide at 4 linkage sites.1,2,3 The molecular weight of EPO is reported to range from 30,000–38,000 daltons.1,2,4 The carbohydrate chains of EPO comprise about 40% of its molecular weight. EPO circulates in plasma with a half-life of approximately 7–8 hours.5 Diurnal fluctuations of plasma EPO levels were reported to occur in residents who live at a high altitude and patients with sleep apnea or lung disease. 6,7,8,9. EPO is the primary regulator of erythropoiesis, stimulating the proliferation and differentiation of erythyroid precursor cells in bone marrow. In mammals, the fetal liver produces nearly all of the hormone. In adults, hepatic production drops to under 10% and renal secretion accountsfor over 90%.10,11 The clearance of circulating EPO is primarily accomplished by uptake into target cells in bone marrow.12,13 Urinary excretion and hepatic elimination also play a role. EPO adjusts red blood cell production to meet tissue oxygen demand. It exerts its effect in a complex feedback system, in which renal secretion of the hormone is controlled by the hypoxia-inducible transcription factors (HIFs).13,14 Low oxygen pressure during hypoxia causes increases in HIFs, which in turn stimulates production of EPO. Under conditions of increased peripheral oxygen, α-subunits of HIFs undergo rapid degradation and EPO levels decrease.5,13
FERRITIN
Ferritin is a compound composed of iron molecules bound to apoferritin, a protein shell. Stored iron represents about 25% of total iron in the body, and most of this iron is stored as ferritin.1 Ferritin is found in many body cells, but especially those in the liver, spleen, bone marrow, and in reticuloendothelial cells.2 Ferritin plays a significant role in the absorption, storage, and release of iron. As the storage form of iron, ferritin remains in the body tissues until it is needed for erythropoiesis. When needed, the iron molecules are released from the apoferritin shell and bind to transferrin, the circulating plasma protein that transports iron to the erythropoietic cells.3 Although dietary iron is poorly absorbed, the body conserves its iron stores carefully, reabsorbing most of the iron released from the breakdown of red blood cells. As a result, the body normally loses only 1–2 mg of iron per day, which is generally restored by the iron absorbed in the small intestine from dietary sources.1 Ferritin is found in serum in low concentrations and is directly proportional to the body’s iron stores.1 Serum ferritin concentration, when analyzed with other factors such as serum iron, iron-binding capacity, and tissue iron stores, is valuable in the diagnosis of iron-deficiency anemias, anemias of chronic infection, and conditions such as thalassemia and hemochromatosis that are associated with iron overload. Measurement of serum ferritin is particularly valuable in distinguishing iron-deficiency anemias caused by low iron stores from those resulting from inadequate iron utilization.1
FOLATE
Folates are compounds of pteroylglutamic acid (PGA) that function as coenzymes in metabolic reactions involving the transfer of single-carbon units from a donor to a recipient compound. Folate, with vitamin B12, is essential for DNA synthesis, which is required for normal red blood cell maturation.1 Humans obtain folate from dietary sources including fruits, green and leafy vegetables, yeast, and organ meats.2 Folate is absorbed through the small intestine and stored in the liver. Low folate intake, malabsorption as a result of gastrointestinal diseases, pregnancy, and drugs such as phenytoin are causes of folate deficiency.3 Folate deficiency is also associated with chronic alcoholism.4 Folate and vitamin B12 deficiency impair DNA synthesis, causing macrocytic anemias. These anemias are characterized by abnormal maturation of red blood cell precursors in the bone marrow, the presence of megaloblasts, and decreased red blood cell survival.1
HEMOPEXIN
Homocysteine (HCY) is a naturally occurring amino acid that is formed from methionine as a product of numerous S‑adenosylmethionine-dependent transmethylation reactions. The metabolism of HCY is regulated by 3 enzymatic pathways that either convert HCY into cysteine or remethylate it back into methionine.1 Homocysteine readily forms disulfide bonds and is present in plasma in 3 forms: free or unbound HCY (1%–2%), homocysteine-cysteine or homocysteine dimers (10%–20%), or protein-bound (> 80%).2 Total plasma homocysteine (HCY), free and bound, is commonly referred to as either homocysteine or homocyst(e)ine.
HOMOCYSTEINE
Homocysteine is an amino acid produced by the body by chemically altering adenosine. Amino acids are naturally made products, which are the building blocks of all the proteins in the body. Most labs report normal ranges of homocysteine as about 4-15 µml/L
IRON
Iron is distributed in the body in such compartments as hemoglobin, tissue, myoglobin, and a labile pool, with the largest amount of iron being found in the hemoglobin of red blood cells or their precursors in bone marrow.1 Approximately 2.5 mg of physiologic iron is found in plasma, as compared to the approximate 2.5 g of iron contained in hemoglobin.2 Disorders of iron metabolism include iron deficiency anemia and iron overload conditions such as hemosiderosis, hemochromatosis, and sideroblastic anemia.2
RBC FOLATE
Iron deficiency causes a rise in the levels of soluble TfR in human blood which is proportional to the extent of the iron deficiency in the tissue (= functional iron deficiency). Cellular TfR binds transferrin and is responsible for tissue iron uptake. The sTfR concentrations remain unchanged until the reserves of storage iron are exhausted (corresponding to a serum ferritin concentration of less than 12 µg/L). Any further reduction in the levels of iron results in a functional iron deficiency which is indicated by a proportional rise in sTfR prior to the occurrence of a significant drop in hemoglobin concentration. Furthermore, the sTfR concentrations rise in relation to the increase in erythrocyte precursor cells (hyperregenerative erythropoiesis)1,2
SOLUBLE TRANSFERRIN RECEPTOR (sTfR)
Iron uptake into cells is mediated through internalizing iron-transferrin complexes. The iron-transferrin complex binds to transferrin receptors present on the external face of the plasma membrane, and is internalized through endosomes with ultimate release of iron into the cytoplasm. Plasma membrane-bound transferrin receptor is released by proteolytic cleavage of the extracellular domain, resulting in the formation of a truncated soluble transferrin receptor (sTfR) that circulates freely in the blood.
The concentration of sTfR is an indicator of iron status. Iron deficiency causes overexpression of transferrin receptor and sTfR levels, while iron repletion results in decreased sTfR levels. While ferritin measurement is the accepted method for assessment of iron deficiency, ferritin is an acute-phase reactant and elevates in response to processes that do not correlate with iron status, including inflammation, chronic disease, malignancy, and infection. sTfR is not an acute-phase reactant and the interpretation of iron status using sTfR measurement is not affected by these confounding pathologies.
TOTAL IRON-BINDING CAPACITY (TIBC)
This assay measures total iron binding capacity in a sequential process that is monitored spectrophotometrically. The sample is added to an acidic Reagent 1 (R1) containing iron and an iron binding dye. Bound iron is released by the acidic R1. Neutral Reagent 2 (R2) buffer is added and the shift in pH allows iron to bind and saturate the transferrin from the sample. The decrease in absorbance is directly proportional to the iron binding capacity of the serum sample.
VITAMIN B12
Vitamin B12, or cyanocobalamin, is a complex corrinoid compound containing 4 pyrrole rings that surround a single cobalt atom.1 Humans obtain vitamin B12 exclusively from animal dietary sources, such as meat, eggs, and milk.2 Vitamin B12 requires intrinsic factor, a protein secreted by the parietal cells in the gastric mucosa, for absorption. Vitamin B12 and intrinsic factor form a complex that attaches to receptors in the ileal mucosa, where proteins known as trans-cobalamins transport the vitamin B12 from the mucosal cells to the blood and tissues.3,4 Most vitamin B12 is stored in the liver as well as in the bone marrow and other tissues. Vitamin B12 and folate are critical to normal DNA synthesis, which in turn affects erythrocyte maturation.3 Vitamin B12 is also necessary for myelin sheath formation and maintenance.2 The body uses its B12 stores very economically, reabsorbing vitamin B12 from the ileum and returning it to the liver so that very little is excreted.4,5
CBC
A complete blood count (CBC) is a blood test used to evaluate your overall health and detect a wide range of disorders, including anemia, infection and leukemia.
A complete blood count test measures several components and features of your blood, including:
-Red blood cells, which carry oxygen
-White blood cells, which fight infection
-Hemoglobin, the oxygen-carrying protein in red blood cells
-Hematocrit, the proportion of red blood cells to the fluid component, or plasma, in your blood
-Platelets, which help with blood clotting
Abnormal increases or decreases in cell counts as revealed in a complete blood count may indicate that you have an underlying medical condition that calls for further evaluation.
TOTAL IgE
The total IgE test measures the overall quantity of immunoglobulin E in the blood, not the amount of a specific type. It can be used to detect an allergic response in the body rather than a specific allergy. This test may compliment the information provided by allergy tests that detect allergen-specific IgE.
TOTAL IgE CATEGORY ANIMALS
Background: Laboratory animal workers are at high risk of developing occupational allergy. In many cases the severity of allergy symptoms makes further work with laboratory animals impossible.
Objective: This study was designed to estimate prevalence rates of sensitization and symptoms of allergy in a population of laboratory animal workers and to determine the association between various host factors and these prevalence rates.
Methods: A cross-sectional survey was undertaken in 540 workers at eight facilities in the Netherlands. All participants completed a questionnaire and underwent skin prick testing with common and occupational allergens. In addition, total and specific IgE measurements were obtained.
Results: Prevalence rates of allergy symptoms caused by working with rats and mice were 19% and 10%, respectively. Symptoms, especially chest tightness, were strongly related to sensitization. Rat and mouse allergy, defined as symptoms of allergy accompanied by specific atopic sensitization, were highly associated with elevated total IgE, reported adverse reactions, and positive skin prick test responses to common allergens. This relationship could be explained by a response to cat or dog allergens.
Conclusions: Allergy to cats or dogs seemed to be an important risk factor for laboratory animal allergy, whereas allergy to pollen or house dust mite, in the absence of cat and dog allergy, appeared to be insignificant. More conclusive evidence about cat and dog allergy preceding laboratory animal allergy can only be provided after analysis of follow-up data.
TOTAL IgE CATEGORY GRASSES
Abstract
Background: Allergy to taxonomically related species is a common phenomenon caused by the same immunological receptor cross-reacting to homologous allergens from different species. Knowledge of patterns of cross-reactivity is crucial for the selection of optimal products for diagnosis and for specific immunotherapy. The objective of this study was to investigate patterns of serum IgE cross-reactivity towards pollens from various grass species.
Methods: With grass group 1 allergens as the representative group, amino acid sequence alignment, structural modelling and comparison of 3D surface characteristics were performed to exemplify the molecular basis of IgE cross-reactivity. IgE binding to extracts from ten different grass species was determined (total number of data pairs >19,000), and IgE inhibition experiments using Phleum pratense were performed.
Results: Analysis of surface topography for group 1 grass allergens demonstrated ample space for IgE binding epitopes in surface areas conserved among Pooideae grasses. Significant correlation was observed between the serum IgE response to P. pratense extract and extracts from the other Pooideae grasses analyzed. P. pratense extract was demonstrated to inhibit the binding of IgE to the allergens in all of the extracts included in the investigation, indicating patient IgE to be primarily directed towards common epitopes.
Conclusion: Extensive IgE cross-reactivity was observed towards the allergens of the Pooideae grasses, meaning that the immune system does not appear to distinguish based on the IgE level between the different species of this subfamily. The data suggest equal effect upon use of any of the Pooideae species for diagnostic as well as therapeutic purposes.
TOTAL IgE CATEGORY HOUSE DUST
Clinical manifestations of immediate hypersensitivity (allergic) diseases are caused by the release of proinflammatory mediators (histamine, leukotrienes, and prostaglandins) from immunoglobulin E (IgE)-sensitized effector cells (mast cells and basophils) when cell-bound IgE antibodies interact with allergen.
In vitro serum testing for IgE antibodies provides an indication of the immune response to allergen(s) that may be associated with allergic disease.
The allergens chosen for testing often depend upon the age of the patient, history of allergen exposure, season of the year, and clinical manifestations. In individuals predisposed to develop allergic disease(s), the sequence of sensitization and clinical manifestations proceed as follows: eczema and respiratory disease (rhinitis and bronchospasm) in infants and children less than 5 years due to food sensitivity (milk, egg, soy, and wheat proteins) followed by respiratory disease (rhinitis and asthma) in older children and adults due to sensitivity to inhalant allergens (dust mite, mold, and pollen inhalants).
TOTAL IgE CATEGORY INSECTS
Background: Detection of specific IgE for Hymenoptera venoms and skin tests are well established diagnostic tools for the diagnosis of insect venom hypersensitivity. The aim of our study was to analyze the effect of total IgE levels on the outcome of generalized anaphylactic reactions after a Hymenoptera sting.
Methods: Two hundred and twenty patients allergic to bee, wasp, or European hornet venom were included in the study. Their specific and total IgE levels, serum tryptase levels, skin tests, and sting history were analyzed.
Results: In patients with mild reactions (grade I, generalized skin symptoms) we observed higher total IgE levels (248.0 kU/l) compared to patients with moderate reactions (grade II, moderate pulmonary, cardiovascular, or gastrointestinal symptoms; 75.2 kU/l) and severe reactions (grade III, bronchoconstriction, emesis, anaphylactic shock, or loss of consciousness; 56.5 kU/l; P < 0.001). Accordingly, 25% of the patients with low levels of total IgE (<50 kU/l), but no individual with total IgE levels >250 kU/l, developed loss of consciousness (P = 0.001). Additionally, specific IgE levels were related to total IgE levels: Specific IgE levels increased from 1.6 to 7.1 kU/l in patients with low (<50 kU/l) and high (>250 kU/l) total IgE levels, respectively (P < 0.001). Specific IgE levels correlated inversely to the clinical reaction grades, however, this trend was not statistically significant (P = 0.083).
Conclusion: Patients with Hymenoptera venom allergy and high levels (>250 kU/l) of total IgE, predominantly develop grade I and grade II reactions and appear to be protected from grade III reactions. However, this hypothesis should be confirmed by extended studies with sting challenges.
SARS-CoV-2 IgG
SARS-CoV-2 IgG (COV2G) assay is a chemiluminescent immunoassay intended
for qualitative and semi-quantitative detection of IgG antibodies to SARS-CoV-2 in human
serum and plasma (potassium EDTA and lithium heparin) using the Atellica® IM Analyzer. The
Atellica IM SARS-CoV-2 IgG (COV2G) assay is intended for use as an aid in identifying
individuals with an adaptive immune response to SARS-CoV-2, indicating recent or prior
infection. At this time, it is unknown for how long antibodies persist following infection and if
the presence of antibodies confers protective immunity. The Atellica IM SARS-CoV-2 IgG
(COV2G) assay should not be used to diagnose acute SARS-CoV-2 infection. Testing is limited
to laboratories certified under the Clinical Laboratory Improvement Amendments of 1988
(CLIA), 42 U.S.C 263a, that meet requirements to perform moderate or high complexity tests
SARS-CoV-2
SARS-CoV-2 is a member of a large family of viruses called coronaviruses. These viruses can infect people and some animals. SARS-CoV-2 was first known to infect people in 2019. The virus is thought to spread from person to person through droplets released when an infected person coughs, sneezes, or talks.