Autoimmune & Inflammation

Autoimmune & Inflammation

Ininfectious mononucleosis, LD is usually more elevated than AST, and there is usually an isomorphic pattern of LD isoenzymes. Inviral hepatitis, by contrast, AST and ALT (the transaminases) are much more increased than is LD, about three or more times higher than total LD, and LD5is high. The differential diagnosis of acute infarct of myocardium includes pericarditis and angina, entities in which enzymes are usually not substantially increased. Bovine or porcine heparin therapy can cause increases of AST, ALT, and LD, with elevated LD hepatic fractions.2

Autoimmune & Inflammation

Elevations in fibrinogen, α- and β-globulins (acute phase reactants), and immunoglobulins increase the sedimentation rate of red cells through plasma. The test is important in the diagnosis of temporal arteritis, as well as its management.1

Autoimmune & Inflammation

Offered as part of multiple lab tests

Autoimmune & Inflammation

Rheumatoid factors are antibodies directed against the Fc fragment of IgG. These are usually IgM antibodies, but may be IgG or IgA. Rheumatoid factor is present in the serum of a majority of patients with rheumatoid arthritis, depending in part on what method is used. Latex beads coated with human IgG will be positive in 70% to 85% (and have significant numbers of false-positives). Sheep RBCs coated with rabbit IgG will be positive in 60% to 70% (and have fewer false-positives). Many rheumatic conditions and other chronic inflammatory processes also may produce rheumatoid factors. The presence of rheumatoid factor, especially in low titer, is far from diagnostic for rheumatoid arthritis. Furthermore, with increasing age, people with no clinical illness may have rheumatoid factor. The presence of IgM RFs has been reported in as much as 10% of the normal population. Statistically, patients with rheumatoid arthritis who have high titer rheumatoid factor are more likely to have severe disease and systemic involvement than other patients. Rheumatoid factor can be detected in synovial fluid, pleural fluid, and pericardial fluid, but contributes little more than a positive serum test. Some rheumatoid factors may behave as cryoglobulins.

Autoimmune & Inflammation

The indirect immunofluorescent test has three elements to consider in the result:1. Positive or negative fluorescence. A negative test is strong evidence against a diagnosis of SLE but not conclusive.2. The titer (dilution) to which fluorescence remains positive (provides a reflection of the concentration or avidity of the antibody). Many individuals, particularly the elderly, may have low titer ANA without significant disease substantiated after work-up.3. The pattern of nuclear fluorescence (reflecting specificity for various diseases). Homogenous and/or nuclear rim (peripheral) pattern correlates with antibody to native DNA and deoxynucleoprotein and bears correlation with SLE, SLE activity, and lupus nephritis. Homogenous (diffuse) pattern suggests SLE or other connective tissue diseases. Speckled pattern correlates with antibody to nuclear antigens extractable by saline; it is found in many disease states, including SLE and scleroderma. When antibodies to DNA and deoxyribonucleoprotein are present (rim and homogenous pattern), there may be interference with the detection of speckled pattern. Nucleolar pattern is seen in sera of patients with progressive systemic sclerosis and Sjögren's syndrome. Centromere pattern is seen in CREST syndrome.Antinuclear AntibodyANA Pattern IdentificationFound InFollow-up TestsSmooth (homogeneous)SLEAnti-dsDNAAnti-ssDNAAnticardiolipinDrug-induced lupus (DIL) other collagen diseases: chronic active hepatitis systemic sclerodermaAntihistoneAntichromatinRFScl-70SS-A/SS-BImmune complexSpeckledSLEAnti-dsDNAAnti-SmAnticardiolipinSjögren's syndromeAnti-SS-A/SS-BAntihistoneViral or induced lupusMCTDAnti-RNPRARFNucleolarPSS/SclerodermaAnti-RNPScl-70Anti-SS-A/SS-BSjögren's syndromeAnti-SS-A/SS-BSubcutaneous SLEImmune complexSLEAnti-dsDNAAnti-ssDNACentromereSclerodermaSS-A/SS-BScl-70CREST syndromeScl-70Anti-RNPFive percent of the apparently "normal population" demonstrate serum ANA. Low titers of ANA reactivity may be seen in patients with rheumatoid arthritis (40% to 60% of patients), scleroderma (60% to 90%), discoid lupus, necrotizing vasculitis, Sjögren's syndrome (80%), chronic active hepatitis, pulmonary interstitial fibrosis, pneumoconiosis, tuberculosis, malignancy, age over 60 (18%), as well as in SLE, especially if the disease is inactive or under treatment. Titers ≥1:160 usually indicate the presence of active SLE, although occasionally other autoimmune disease may induce these high titers. There are now known groups of "ANA-negative" lupus patients. Such patients often have antibodies to SS-A/Ro antigen (usually when a frozen section substrate is used) and subacute cutaneous lupus. Ten percent of patients with SLE manifest biologic false-positive tests for syphilis; this may even be the initial manifestation. Some other tests used in differentiation of autoimmune states include antibody to double-stranded DNA, rheumatoid factor, antibody to extractable nuclear antigens, total hemolytic complement (C3, C4, etc). Although ANA tests are occasionally ordered on cerebrospinal fluid or synovial fluid, the current assays are not standardized for these fluids and such assays do not add to the diagnostic process.

Autoimmune & Inflammation

LH (luteinizing hormone), together with FSH (follicle-stimulating hormone), belongs to the gonadotropin family. LH and FSH regulate and stimulate the growth and function of the gonads (ovaries and testes) synergistically.2-4Like FSH, TSH, and hCG, LH is a glycoprotein consisting of two subunits (α- and β-chains). This proteohormone, which consists of 121 amino acids3and three sugar chains, has a molecular weight of 29,500 daltons.4In women, the gonadotropins act within the hypothalamus-pituitary-ovary regulating circuit to control the menstrual cycle.5,6LH and FSH are released in pulses from the gonadotropic cells of the anterior pituitary and pass via the bloodstream to the ovaries. Here the gonadotropins stimulate the growth and maturation of the follicle and hence the biosynthesis of estrogens and progesterones. The highest LH-concentrations occur during the midcycle peak and induce ovulation and formation of the corpus luteum, the principal secretion product of which is progesterone.Determination of LH concentration is used in the elucidation of dysfunctions within the hypothalamus-pituitary-gonads system. In the Leydig cells of the testes, LH stimulates the production of testosterone.The determination of LH in conjunction with FSH is utilized for the following indications: congenital diseases with chromosome aberrations (eg, Turner syndrome), polycystic ovaries (PCO), clarifying the causes of amenorrhea, menopausal syndrome, and suspected Leydig cell insufficiency.2,5,6

Autoimmune & Inflammation

FSH is a glycoprotein consisting of two subunits (α- and β-chains). Its molecular weight is approximately 32,000 daltons. FSH together with LH (luteinizing hormone), belongs to the gonadotropin family. FSH and LH regulate and stimulate the growth and function of the gonads (ovaries and testes) synergistically.3FSH and LH are released in pulses from the gonadotropic cells of the anterior pituitary. The levels of the circulating hormones are controlled by steroid hormones via negative feedback to the hypothalamus. In the ovaries, FSH, together with LH, stimulates the growth and maturation of the follicle and hence also the biosynthesis of estrogens in the follicles.In women, the gonadotropins act within the hypothalamus-pituitary-ovary regulating circuit to control the menstrual cycle.1,4The FSH level shows a peak at midcycle, although this is less marked than with LH. Due to changes in ovarian function and reduced estrogen secretion, high FSH concentrations occur during menopause.1The determination of FSH in conjunction with LH is utilized for the following indications: congenital diseases with chromosome aberrations, polycystic ovaries (PCO), amenorrhea (causes), and menopausal syndrome.In men, FSH serves to induce spermatogonium development. Determination of the FSH concentration is used in the elucidation of dysfunctions within the hypothalamus-pituitary-gonads system. Depressed gonadotropin levels in men occur in azoospermia.1,3,5,6

Autoimmune & Inflammation, Hormone Testing

Thyroglobulin antibody (TgAb) measurement is typically used in two clinical scenarios, in the assessment of autoimmunity and in the follow-up of patients treated for differentiated thyroid carcinoma (DTC).1-8In thyroid autoimmunity, TgAb level can be increased. However, the presence of TgAb is not always pathogenic nor diagnostic, especially at very low levels. Because changes in TgAb levels can reflect changes in thyroid tissue mass, TgAb concentrations can also serve as a surrogate tumor marker for DTC recurrence and for monitoring changes in tumor mass in certain patients.1A rising, or de novo appearance of TgAb may indicate recurrence, whereas a progressive decline suggests successful treatment.3When present, TgAb interferes with thyroglobulin (Tg) measurement, causing falsely low or undetectable Tg immunometric assay values that can mask disease. Guidelines mandate that every Tg test have TgAb measured simultaneously and quantitatively by immunoassay. The propensity and magnitude of TgAb-Tg interference relates to both Tg and TgAb concentrations and the class of Tg method used.The United States NHANES III survey reported a TgAb prevalence of approximately 10% for the general population, measured by competitive immunoassay.1This study reported that 3% of subjects with no risk factors for thyroid disease had detectable TgAb without associated presence of thyroid peroxidase (TPO) antibodies.1TgAb prevalence has been shown to be approximately twofold higher than normal for patients diagnosed with disseminated thyroid carcinoma (~20%).2,3It has been suggested that low levels may represent "natural" antibody in healthy individuals or, alternatively, may represent underlying silent autoimmune thyroid disease.4There is some debate over the clinical utility of serum TgAb measurement for assessing the presence of thyroid autoimmunity in areas of iodide sufficiency.4,5In iodide-deficient areas, however, TgAb is believed to be useful for detecting autoimmune thyroid disease, especially for patients with a nodular goiter. TgAb measurements are also useful for monitoring iodide therapy for endemic goiter, since iodinated Tg molecules are more immunogenic. Sera samples were obtained in the United States for males <30 years of age following the criteria outlined by the National Academy of Clinical Biochemists (NACB) for establishing a normal reference range for thyroid tests.6,7The screening criteria included serum TSH levels between 0.5 and 2.0 mIU/L, no personal or family history of thyroid disease, and absence of nonthyroid autoimmune disease. One hundred thirty-seven screened samples were tested, generating a 95% nonparametric upper reference limit below 4 IU/mL. Additionally, 519 samples were collected in the United States for both males and females ranging from 18 to 74 years of age. The screening criteria included serum TSH levels between 0.5 and 2.0 mIU/L, no personal or family history of thyroid disease, and absence of nonthyroid autoimmune disease. Of the 519 samples tested, 96% fell below 4 IU/mL.Labcorp reports TgAb results above the limit of detection as elevated. The decision to employ this threshold is based on the fact that the presence of TgAb above the limit of detection is suggestive of the presence of thyroid tissue and can be a negative prognostic in patients treated for DTC. Also, the presence of any level of TgAb in cases where Tg testing is ordered causes the lab to employ an alternate method for that measurement; one that is not confounded by TgAb.

Autoimmune & Inflammation, Infectious Diseases

Increased monoclonal IgA may be produced in lymphoproliferative disorders, especially multiple myeloma and “Mediterranean” lymphoma involving bowel. An IgA monoclonal peak >2 g/dL is a major criterion for myeloma. It may be elevated in a wide range of conditions affecting mucosal surfaces, where IgA is largely produced. Some clinically significant IgA deficiencies have concomitant deficiencies of IgG2and IgG4. IgA may be decreased in patients with chronic sinopulmonary disease, in ataxia-telangiectasia, or congenitally. Patients with congenital IgA deficiency are prone to autoimmune diseases, and may develop antibody to IgA and anaphylaxis if transfused. IgA levels may rise with exercise and fall during pregnancy.

Autoimmune & Inflammation

The concentration of IgE in serum of normal individuals typically represents <0.001% of the total immunoglobulins present.1,2Immunoglobulins of the IgE class play an important role in mediating the atopic reactions that occur when sensitive individuals are exposed to allergens. IgE has a structure that is similar to other immunoglobulins in that it consists of four chains: two light chains and two heavy chains.1The heavy chains for each IgE molecule contain a variable region that accounts for antigen specificity. Since IgE myeloma is extremely rare, the clinical utility of measuring IgE levels generally involves its role as the mediator of the allergic response. The majority of IgE molecules in serum are bound to the surface of mast cells and basophilic granulocytes. The interaction of allergens with the cell-bound allergen-specific IgE causes these cells to release histamines and other vasoactive substances, thereby initiating the allergic reaction. Approximately 50% of individuals with allergic rhinitis or asthma will have elevated levels of IgE;1however, a large number of individuals with allergy and elevated levels of IgE to specific allergens will have normal levels of total IgE. Studies have indicated that total IgE levels are often elevated in patients with atopic dermatitis and the concentration of IgE tends to correlate with severity of eczema.1Total IgE levels can also be elevated in patients with parasitic infections, allergic bronchopulmonary aspergillosis, or immunodeficiency.1,2

Autoimmune & Inflammation

Positive direct antiglobulin tests are associated with a variety of conditions which include hemolytic transfusion reaction, autoimmune hemolytic anemia, hemolytic disease of the fetus/newborn, and may be secondary to certain pathological conditions or drug therapy.Note:The presence of a positive direct antiglobulin test does not necessarily correlate with a pathological condition.

Autoimmune & Inflammation

Offered as part of multiple lab tests

Autoimmune & Inflammation

CRP is a pentameric globulin with mobility near the γ zone. It is an acute phase reactant which rises rapidly, but nonspecifically in response to tissue injury and inflammation. It is particularly useful in detecting occult infections, acute appendicitis, particularly in leukemia and in postoperative patients. In uncomplicated postoperative recovery, CRP peaks on the third postop day, and returns to preop levels by day seven. It may also be helpful in evaluating extension or reinfarction after myocardial infarction, and in following response to therapy in rheumatic disorders. It may help to differentiate Crohn's disease (high CRP) from ulcerative colitis (low CRP), and rheumatoid arthritis (high CRP) from uncomplicated lupus (low CRP).

Autoimmune & Inflammation

Offered as part of multiple lab tests

Autoimmune & Inflammation

Antibodies to DNA, either single- or double-stranded, are found primarily in systemic lupus erythematosus, and are important, but not necessary or sufficient for diagnosing that condition. Such antibodies are present in 80% to 90% of SLE cases. They are also present in smaller fractions of patients with other rheumatic disorders, and in chronic active hepatitis, infectious mononucleosis, and biliary cirrhosis.In the past, it was considered unnecessary to test for anti-DNA in patients with a negative test for antinuclear antibodies. A group of “ANA-negative lupus” patients has been described with anti-ssDNA and anti-SS-A/Ro and anti-SS-B/La; however, HEp-2 substrate is much more sensitive than frozen section substrates, and it is uncommon for anti-SS-A/Ro to be negative with these newer substrates.This standard dsDNA detects both low- and high-affinity antibodies, providing a very sensitive test for diagnostic purposes; however, it is less predictive for severe nephritis, which is associated with the presence of high-affinity antibodies.Following levels of anti-DNA antibody may be of use in evaluating response to therapy, but should be regarded as a guide rather than a rigid dictator of treatment. Antibody levels correlate particularly well with activity of lupus nephritis.Procainamide and hydralazine may induce anti-DNA antibodies and antihistone antibodies.

Autoimmune & Inflammation

Immunoglobulin G is the major antibody containing protein fraction of blood. With significant decreases in IgG level, on either a congenital or acquired basis, there is an increased susceptibility to infectious processes ordinarily dealt with by humoral antibody (ie, bacterial infection). Thus, patients with repeated infection should have their immunoglobulins, and specifically IgG, measured. Therapy with exogenous γ-globulins may be efficacious in such patients. Conversely, IgG levels will be increased in immunocompetent individuals responding to a wide variety of infections or inflammatory insults (indeed, this represents the basis of the serologic diagnosis of infectious diseases). IgG specific antibody can now be demonstrated for numerous organisms, and when coupled with IgM specific antibody, can give an accurate diagnosis of acute or chronic infection. Today, a major cause for a polyclonal increase in IgG is the acquired immunodeficiency syndrome. Monoclonal IgG can be demonstrated in many cases of multiple myeloma. 3 g/dL of monoclonal IgG is a major diagnostic criterion for myeloma. Oligoclonal IgG can be seen in multiple sclerosis and some chronic hepatitides.A monoclonal gammopathy may be present when the total IgG value is in the normal range. While many of these patients do not have multiple myeloma, evaluation of these patients for evaluation of the gammopathy and the presence of Bence Jones protein in urine is important.

Autoimmune & Inflammation

Antibodies to thyroid microsomes (thyroid peroxidase) are present in 70% to 90% of patients with chronic thyroiditis. They are also present in smaller percentages of patients of other thyroid diseases. Antibody production may be confined to lymphocytes within the thyroid, and serum may be negative. Small numbers (3%) of people with no evidence of disease may have antibody. This is more frequent in females and increases with age.

Autoimmune & Inflammation

Offered as part of multiple lab tests

Autoimmune & Inflammation

C3comprises about 70% of the total protein in the complement system and is central to activation of both the classical and alternate pathways. Increased levels are found in numerous inflammatory states as an acute phase response. CH50(total complement hemolytic activity), C3and/or C4may be decreased in cases of systemic lupus erythematosus, especially in cases with lupus nephritis, acute and chronic hypocomplementemic nephritis, subacute bacterial endocarditis, DIC, and partial lipodystrophy (with associated nephritis-like activity in serum.) In cases of disseminated intravascular coagulation, plasmin attacks C3directly, and C3levels have been found low in the hemolytic uremic syndrome form of disseminated intravascular coagulation (DIC). Cases of hereditary C3deficiency, while rare, have been reported and are characterized clinically by recurrent infections (eg, pneumonia, meningitis, paronychia, impetigo). Pathogenic bacteria causing infections in these cases have included both gram-positive and gram-negative organisms. C3levels have also been found deficient in cases of uremia, chronic liver diseases, anorexia nervosa, and celiac disease.

Autoimmune & Inflammation

C4is used only by the classical pathway, so that it is decreased only when this arm is activated. In diseases activating the alternate pathway alone, C4levels will be normal. Total hemolytic activity (CH50), C3, and C4are frequently decreased in a variety of conditions producing immune complexes. C4levels are sensitive indicators of lupus disease activity. In hereditary angioedema, the lack of C1esterase inhibitor allows unopposed lysis of C2and C4by C1esterase, so C4levels will be low. C4deficiency has been described in association with a clinical SLE-like disease but with absence of LE cells and variable immunoglobulin or C3deposits in the skin biopsy, and with Henoch-Schönlein purpura or glomerulonephritis. The condition is inherited as an autosomal recessive trait with close HLA linkage. Hereditary C4deficiency has been associated with an increased incidence of pyogenic bacterial infections.

Autoimmune & Inflammation

Actin antibodies are found in 52% to 85% of patients with autoimmune hepatitis or chronic active hepatitis and in 22% of patients with primary biliary cirrhosis.

Autoimmune & Inflammation

Other abnormalities found in some sarcoidosis patients include elevations of serum alkaline phosphatase, calcium, gamma globulin with polyclonal gammopathy, and hypercalciuria. Serum angiotensin converting enzyme is elevated in 50% of cases of sarcoidosis but not in cases of active tuberculosis or Hodgkin disease. Increases are less frequent when sarcoidosis is inactive.6Some 80% to 90% of patients with demonstrably active sarcoidosis have elevated serum ACE. Angiotensin converting enzyme activity is also increased in sarcoid lymph node homogenate. The diagnosis of sarcoidosis is an histopathologic/clinical complex. Noncaseating granulomas must be proven not to be caused by tuberculosis, histoplasmosis, or other microbiologic entities. Berylliosis is a very rare cause of such granulomas.ACE is a dipeptidyl carboxypeptidase. It functions to split dipeptides from the free carboxy end of a variety of polypeptides including angiotensin I and bradykinin. It is especially known for its generation of the octapeptide angiotensin II by releasing the dipeptide histidyl-leucine from angiotensin I. The major site of ACE production is the pulmonary bed of endothelial cells.Thyroid hormone may modulate ACE activity. Both patients with low T3levels (and clinical hypothyroidism) and patients with anorexia nervosa with associated findings of hypothyroidism may have low serum ACE activity.7,8Monitoring of ACE levels may have application in assessing risk of pulmonary damage due to use of some antineoplastic agents, in particular bleomycin.9Serum ACE is decreased in some patients with bronchogenic carcinoma. With response to chemotherapy/radiation therapy the ACE level has been noted to normalize.10Cerebrospinal fluid ACE is useful in patients with neurosarcoidosis.Elevated serum ACE levels in a case of the uncommon entity, Melkersson-Rosenthal syndrome, probably relate to the sarcoid-like noncaseating granulomas that are found in this condition. ACE levels normalized after successful (clinical management) therapy with methotrexate.11Serum ACE abnormality has been reported in 20% to 30% of alpha1-antitrypsin variants (MZ, ZZ, and MS Pi types) but in only about 1% of individuals with normal MM Pi type.12There is evidence that paraquat poisoning (because of its effect on pulmonary capillary endothelium) is associated with elevated serum ACE.13

Autoimmune & Inflammation, Infectious Diseases

Useful in differentiating inflammatory and neoplastic diseases and as an index of disease severity. CRP is also useful in monitoring inflammatory disease states.

Autoimmune & Inflammation

Offered as part of multiple lab tests

Autoimmune & Inflammation

The complement component 1q (or simply C1q) is a protein complex involved in the complement system, which is part of the innate immune system. C1q together with C1r and C1s form the C1 complex.1

Autoimmune & Inflammation

Deficiencies of C1components, C2and C4are associated with rheumatic diseases, including lupus, vasculitis, and dermatomyositis. Some individuals with deficiency may have no evidence of disease. The most common complement deficiency is C2, which is a homozygous abnormality in 1 in 10,000 to 40,000 individuals, and is heterozygous in 1% to 2% of the general population. Patients with C2deficiency and lupus often have negative or low titer ANA.

Autoimmune & Inflammation

Offered as part of multiple lab tests

Autoimmune & Inflammation

Thyrotropin-receptor antibody is an autoantibody to the thyroid cell receptor for thyroid-stimulating hormone. It can be demonstrated in 90% of patients with Graves' disease, and is the cause of the hyperthyroidism of that condition. The characterization of TRA resolved much confusion about long-acting thyroid stimulator (LATS) and LATS protector, which are both, in fact, thyroid-stimulating autoantibodies which simply behaved differently in animal test systems. These antibodies are present in 50% of euthyroid Graves' disease as well as hyperthyroid patients. They play a major role in the pathogenesis of Graves' disease. Detection of these antibodies is useful in prediction of neonatal hyperthyroidism and prediction of relapse of hyperthyroidism.

Autoimmune & Inflammation

Offered as part of multiple lab tests

Autoimmune & Inflammation, Bone Health

Elevated RF is found in collagen vascular diseases such as SLE, rheumatoid arthritis, scleroderma, Sjogren's syndrome, and in other conditions such as leprosy, tuberculosis, syphilis, malignancy, thyroid disease and in a significant percentage of otherwise normal elderly patients.

Autoimmune & Inflammation, Infectious Diseases

Increased CRP levels are found in inflammatory conditions including: bacterial infection, rheumatic fever, active arthritis, myocardial infarction, malignancies and in the post-operative state. This test cannot detect the relatively small elevations of CRP that are associated with increased cardiovascular risk.

Heart Health & Cardiovascular, Autoimmune & Inflammation

Useful in predicting risk for cardiovascular disease.

Autoimmune & Inflammation

Complement is a system of 25 cell membrane associated and plasma proteins, which when activated produce multiple inflammatory mediators, opsonins, lysins, and down regulators vital to the normal function of the immune system. Complement components belong to a “classical” and “alternative” pathway whose activation steps differ. Complement proteins can be increased as part of the acute-phase response to inflammation or infection, and they can be decreased or absent due to hypercatabolism, expenditure in immune complexes, or hereditary deficiency. Patients with hereditary absence of a complement protein may have decreased total complement and recurrent bacterial infections or a rheumatic illness. Conversely, patients with rheumatic diseases, particularly with active illness and activation of complement and formation of immune complexes, may have low total complement. Falling complement levels may presage clinical flares, particularly of lupus nephritis.

Autoimmune & Inflammation, Infectious Diseases

Decreased C3 may be associated with acute glomerulonephritis, membranoproliferative glomerulonephritis, immune complex disease, active systemic lupus erythematosis, and generalized autoimmune processes.

Autoimmune & Inflammation

This test is useful in evaluating patients presenting with sarcoidosis, Gaucher's disease and lymphangiomyomatosis in that the enzyme is increased in these clinical settings.

Autoimmune & Inflammation, Infectious Diseases

Decreased C4 level is associated with acute systemic lupus erythematosis, glomerulonephritis, immune complex disease, cryoglobulinemia, congenital C4 deficiency and generalized autoimmune disease.

Autoimmune & Inflammation

The more common form (85% of patients) of hereditary angioneurotic edema is due to an absolute decrease in the amount of C1esterase inhibitor. A less common form (15% of patients) is due to a functional defect where quantitative levels may be normal. Both abnormalities must be tested for due to the potential life-threatening nature of the illness.In addition to decreased C1esterase inhibitor in the serum of patients with hereditary angioneurotic edema, a unique polypeptide kinin is increased in plasma from C1esterase inhibitor deficient patient during attacks of swelling. Danazol, a synthetic androgenic inhibitor of gonadotropin release, with little virilizing potential, decreases the number of clinical attacks in cases of hereditary angioneurotic edema. Patients with attacks of hereditary angioneurotic edema also have low total complement, C4and C2. Consequently, measurement of serum C4is an often used test. Hereditary angioneurotic edema is transmitted as an autosomal dominant trait. Heterozygotes also show decreased levels of C1esterase inhibitor. During acute attacks of the disease, complement factors C4and C2can be markedly reduced, but C1and C3are normal. The initiating stimulus of clinical attacks is often unknown.Angioedema may also be an acquired illness. The acquired form includes nonhereditary C1esterase deficiency; drug induced, allergic, and idiopathic forms, angioedema associated with autoimmune disease, especially with systemic lupus erythematosus and hypereosinophilia; angioedema occasionally associated with malignancy; and angioedema caused by physical stimuli. Angioedema has occasionally been known to precede development of lymphoproliferative disorders.

Autoimmune & Inflammation, Infectious Diseases

Increased IgA is associated with monoclonal IgA myeloma, respiratory and gastrointestinal infections, and malabsorption; decreased IgA is found in selective IgA deficiency and in ataxia telangiectasia.

Allergy Testing, Autoimmune & Inflammation

Histamine is synthesized from the amino acid L-histidine through the action of the enzyme histidine decarboxylase.1This small molecule is primarily produced by mast cells and basophils. These cells are morphologically characterized by numerous, electron dense cytoplasmic granules, which contain histamine and other compounds, enabling a massive acute release in response to immunologic and non-immunologic stimuli.2-10Mast cells and basophils are critical effectors of local and systemic hypersensitivity reactions and other immediate or chronic inflammatory conditions.11-16Histamine release can be triggered by allergic sensitization or by other stimuli, including cytokines, chemokines, complement components, IgG, microbes, drugs, and toxins through specific receptors expressed by these cells.11-13,16-18In addition to mast cells and basophils, a number of cell types, including gastric enterochromaffin-like cells, histaminergic neurons, platelets, dendritic cells and T cells can produce histamine.1These cells do not store histamine intracellularly but instead secrete it after synthesis.10,19-22Histamine is a central mediator of allergic response. Exposure of sensitized individuals to allergens triggers histamine release by basophil and mast cells. Histamine binds to specific receptors on smooth muscle cells and provokes potent adverse effects. Histamine concentration in biological fluids is correlated with the severity of vascular and respiratory signs of anaphylaxis. Histamine quantification has been used to confirm that clinical signs result from the degranulation of mast cells and/or basophils.23-26This confirmation can support further investigation in order to find the offending allergen against which the patient is sensitized, allowing there after the avoidance of a new anaphylaxis reaction by the specific eviction of the allergen, or aninduction of tolerance. Several other non-immunologic stimuli may also activate mast cells. These stimuli include neuropeptides and complement factors (i.e., C3a and C5a).27Beyond its role in immediate type allergic reactions, histamine is involved in a number of physiological functions, including cell proliferation and differentiation, hematopoiesis, embryonic development, regeneration, and wound healing.6,7,28-30Once released into the circulation, histamine produces many varied effects within the body, including the contraction of smooth muscle tissues of the lungs, uterus, and stomach; the dilation of blood vessels, which increases permeability and lowers blood pressure; the stimulation of gastric acid secretion in the stomach; and the acceleration of heart rate. Histamine also serves as a neurotransmitter, carrying chemical messages between nerve cells.Mast cells have been implicated in the pathogenesis of a broad range of disorders and conditions related to mast cell activation.13,17,31Severe forms of mast cell activation (anaphylaxis) are usually observed in patients with IgE-dependent allergies and those with clonal mast cell disorders.17,32,33A number of predisposing genetic conditions, underlying allergic and other hypersensitivity states, and related comorbidities can contribute to the clinical manifestation of mast cell activation syndromes.31The severity of mast cell activation symptoms depends on several factors, including the type of allergen, the route of exposure, augmenting factors, comorbid conditions, the presence of clonal mast cells, and genetic background. Histamine is released from mast cells during anaphylaxis and increased in biological fluids (plasma, urine) during and shortly after an anaphylactic episode.34Compared to serum tryptase levels, histamine may sometimes be a more sensitive parameter (biomarkers) in allergic reactions and thus also detected as elevated in less severe or chronic forms of mast cell activation but are less specific for the mast cell lineage and less-well validated in mast cell activation contexts compared to tryptase.31,35Histamine is endogenous in numerous foods and excessively high levels can be indicative of defective food processing, microbial activity, and general deterioration.36On the other hand, the presence of histamine in processed foods, such as aged cheeses, is necessary to achieve characteristic flavors and textures. A number of alcoholic beverages contain a significant amount of histamine. In addition, fish can be a food source of histamine, depending on its exposure to microbial contamination or unfavorable storage conditions. Scombroid fish poisoning, also known as histamine fish poisoning, is an allergic-type reaction that occurs within a few hours of eating fish contaminated with high levels of histamine.37When certain types of fish are not properly refrigerated, bacteria in the fish can multiply, break down the flesh of the fish, and produce high amounts of histamine. The most common sources of illness are finfish such as tuna, mackerel, amberjack and bonito. Other fish, such as mahi mahi, bluefish, marlin, and escolar, can also cause scombroid fish poisoning.Histamine intolerance results from a disequilibrium between accumulated histamine and capacity for histamine degradation.38,39Histamine occurs to various degrees in many foods. In healthy persons, dietary histamine can be rapidly detoxified by amine oxidases, whereas persons with low amine oxidase activity are at risk of histamine toxicity. The ingestion of histamine-rich food,alcohol or drugs that release histamine or block amine oxidase activity may provoke diarrhea,headache, rhinoconjunctival symptoms, asthma, hypotension, arrhythmia, urticaria, pruritus,flushing and other conditions in patients with histamine intolerance. Symptoms can be mitigated by a histamine-free diet and/or treatment with antihistamine drugs.

Autoimmune & Inflammation, General Health & Wellness

This immunofluorescence assay (IFA) is often ordered as part of an initial diagnostic evaluation of individuals with clinical suspicion of autoimmune diseases associated with antinuclear antibodies (ANAs). The American College of Rheumatology (ACR) recommends IFA on human epithelial type 2 (HEp-2) cells as the gold standard method for ANA testing because of its overall high sensitivity [1].ANAs are associated with several autoimmune diseases, such as systemic lupus erythematosus, systemic sclerosis, mixed connective tissue disease, polymyositis, primary biliary cholangitis, rheumatoid arthritis, juvenile rheumatoid arthritis, Sjogren syndrome, and autoimmune hepatitis. The laboratory evaluation for individuals with clinical suspicion of these autoimmune diseases often begins with an ANA screen.Knowing the ANA titer can be helpful in interpreting positive ANA results. A titer of at least 1:40 is considered positive, but low-positive titers are not uncommon in healthy individuals. Higher titers are generally associated with greater likelihood of autoimmune disease [2]. When results are positive, various fluorescent staining patterns observed in the nucleus or the cytoplasm can aid in the differential diagnosis and guide selection of further testing for specific autoantibodies. The International Consensus on Antinuclear Antibody Pattern provides guidance on interpretation and reporting of IFA staining patterns with HEp-2 cells [3].Individuals with negative results on the ANA IFA usually also have negative results on specific ANAs. Therefore, subserology testing is generally not recommended in individuals without positive ANA IFA results and clinical suspicion of relevant autoimmune disease [4]. However, Jo-1 antibody may be detected in ANA IFA-negative patients with some types of myositis, and SSA antibody may be detected in some ANA IFA-negative patients with lupus or Sjogren syndrome [4].The results of this test should be interpreted in the context of pertinent clinical and family history and physical examination findings.References1. Methodology of testing for antinuclear antibodies (position statement). 2009. American College of Rheumatology. Updated December 2019. Accessed May 15, 2023.https://assets.contentstack.io/v3/assets/bltee37abb6b278ab2c/blta48818378bc89445/acr-position-statement-methodology-testing-antinuclear-antibodies.pdf2. Tozzoli R, et al.Am J Clin Pathol. 2002;117(2):316-324.3. Chan EK, et al.Front Immunol. 2015;6:412.4. Yazdany J, et al.Arthritis Care Res (Hoboken). 2013;65(3):329-339.

Autoimmune & Inflammation

SS-A(Ro) is found in 60% to 70% of patients with Sjögren's syndrome and 30% to 40% of patients with SLE. SS-B(La) is found in 50% to 60% of Sjögren's syndrome and 10% to 15% of SLE. SS-A cannot be demonstrated by immunofluorescence (it is soluble in the buffers used), but SS-B may be seen as a speckled antinuclear pattern. SS-A and SS-B are particularly useful in “ANA-negative” cases of SLE, being present in a majority of such cases. Patients who are ANA-positive and who have SS-A but not SS-B are very likely to have nephritis. Antibodies to SS-A are also associated with HLA loci DR3 and DR2 and with hereditary deficiency of C2. Anti-SS-A and anti-SS-B are found in virtually all children with neonatal lupus. Patients with SS-A may also have antibodies to cardiolipin, lupus anticoagulant, and clinical thromboses. This has been termed antiphospholipid antibody syndrome.

Autoimmune & Inflammation

Immunoglobulin M is a pentamer of 7S γ-globulin and is an efficient complement binder. It is the antibody type produced initially in the immune response and the first immunoglobulin class to be synthesized by a fetus or newborn. IgM antibodies do not cross the placenta. For these reasons the demonstration of IgM-specific antibody is useful in assessing whether a particular infection is acute (in which case IgM antibodies will be present) or chronic (IgG antibodies will predominate) and whether a newborn has a congenital infection (a newborn with IgM antibody is infected; a newborn with IgG antibody has passively acquired maternal antibody, which simply crossed the placenta). In the hyper-IgM immunodeficiency syndrome, there is an absence of IgG and IgA in serum and a marked increase in IgM. Macroglobulins produced in Waldenström disease are IgM, and may produce hyperviscosity syndrome. More than 2 g/dL of monoclonal IgM is a major diagnostic criterion of myeloma. Increased IgM (with other immunoglobulins) may develop in inflammatory/infectious conditions. IgM is characteristically elevated in primary biliary cirrhosis. The majority of rheumatoid factors are IgM. IgM will be decreased in congenital or acquired hypogammaglobulinemia, and this will be associated with increased, recurrent infection.

Autoimmune & Inflammation

Increased IgM is associated with Waldenström's macroglobulinemia, infectious mononucleosis, viral infections, nephrotic syndrome, and estrogen therapy; decreased IgM is found in selective IgM deficiency, Bruton's Disease, and acquired immune deficiency.

Autoimmune & Inflammation

Measurement of thyroglobulin antibodies is useful in the diagnosis and management of a variety of thyroid disorders including Hashimoto's thyroiditis, Graves' disease and certain types of goiter.

Autoimmune & Inflammation, Infectious Diseases

Increased IgG is associated with acute and chronic inflammations, monoclonal IgG myeloma, autoimmune diseases; decreased IgG is found in selective IgG deficiency, Bruton's Disease, and acquired immune deficiency.

Allergy Testing, Autoimmune & Inflammation

For diagnosis of allergic disease. A normal IgE level does not exclude the possible presence of an allergic disorder.

Autoimmune & Inflammation

Myasthenia gravis (MG) is an acquired disorder of neuromuscular transmission that is characterized by skeletal muscle weakness and fatigability on exertion that is exacerbated by repeated muscle activity.2-7This autoimmune disease is caused by antibodies directed toward receptors embedded in the motor endplate of the neuromuscular junction. Progressive weakness of the ocular muscles manifesting as asymmetric ptosis and variable diplopia are the presenting symptoms in 60% of patients.5,7Many patients progress to more generalized weakness of peripheral limb muscles and muscles required for body posture, including facial and neck muscles. Bulbar muscle weakness compromises speaking (dysarthria), chewing and swallowing (dysphagia) and respiratory muscle weakness can lead to a myasthenic crisis where patients need to be ventilated artificially.8Clinical symptoms may be restricted to one muscle group, in particular the eye muscles (ocular MG), or may become generalized (generalized MG).5-8Patients with MG frequently have thymic abnormalities (thymic hyperplasia or thymoma).9Ten to 15 percent of patients with MG patients have thymoma, and up to 50% of thymoma patients develop MG.9It is thought that the thymus plays a role in MG pathogenesis and these patients respond well to the surgical removal of the thymus gland.10Neonatal MG can occur as a result of trans-placental transit of antibodies from an affected mother to the fetus, or in some cases, due to antibody to the fetal form of AChR.11-13In the latter case, the mother may be unaffected. It should be noted that the AChR antibody assays employed by Labcorp contain a mixture of adult and embryonic AChRs allowing for the detection of autoantibodies to both proteins. In most cases affected babies are born with a diminished ability to suck and generalized hypotonia. Decrease in utero feta movement caused by MG can also result in arthrogryposis multiplex congenital, a condition where the neonate suffers from contractures in more than two joints and in multiple body areas.The majority of patients with MG have antibodies to the acetylcholine receptor (AChR) and, less frequently, to the other proteins at postsynaptic membrane of the neuromuscular junction.14-16AChR antibodies impede neuromuscular transmission by a range of pathogenic mechanisms including the alteration of tissue architecture and/or by causing a reduction the density of functionality of AChRs.1,17-21Three functionally different types of antibodies against muscle AChR can be measured.1,21-24• AChR binding antibodies attach to the AChR activate the complement system result in in destruction and focal lysis of the neuromuscular junction leading to the destruction of AChR and AChR-related protein at the end-plate.1,20• AChR blocking antibodies functionally block the binding of the neurotransmitter acetylcholine to the receptor.20These antibodies usually occur in association with AChR-binding antibodies and have a higher prevalence in generalized MG compared with ocular MG.20• AChR modulation antibodies crosslink receptor subunits in such as way as to cause the receptors to be internalized and degraded in a process known as antigenic modulation.20,22,25-27Modulating antibodies are implicated with an increased risk of thymoma and the majority of patients with thymoma have modulating antibodies.28Test for serum autoantibodies are highly sensitive and specific for generalized MG but lack sensitivity when there is pure ocular involvement.1,14,29-30Approximately 85% of patients with generalized MG have detectable muscle AChR antibodies (of one or more types), while fewer patients with ocular MH have the antibodies (50-60%).4,30In general, an elevated level of any one of the AChR-binding antibodies in a patient with compatible clinical features confirms the diagnosis of MG. Approximately 15 percent of individuals with confirmed myasthenia gravis have no measurable AChR binding, blocking, or modulating antibodies. Thirty-five percent of these patients (six percent of all MG patients) will have antibodies directed against a muscle-specific tyrosine kinase (MuSK).10,31Autoantibodies levels do not generally correlate with disease severity. However, in individual patients, serial antibody titers tend to correlate with disease status.18,19,32-34Autoantibodies directed against the contractile elements of striated muscle are found in 30% of adult patients with myasthenia gravis and in 80% of those with thymoma.35-37Striational antibodies are associated with the late-onset MG subgroup and are rarely found in AChR antibody-negative MG.

Autoimmune & Inflammation

dsDNA Antibody is detected in patients with active systemic lupus erythematosus (SLE) and approximately 20% of patients with Mixed Connective Tissue Disease.

Autoimmune & Inflammation

dsDNA Antibody is detected in patients with active systemic lupus erythematosus (SLE) and approximately 20% of patients with mixed connective tissue disease.

Infectious Diseases, Autoimmune & Inflammation

This test is a sensitive test for recentstreptococcalinfection. A rise in ASO begins about one week after infection and peaks two to four weeks later. ASO levels do not rise with cutaneous infections. In the absence of complications or reinfection, the ASO level will fall to preinfection levels within 6 to 12 months. Over 80% of patients with acute rheumatic fever and 95% of patients with acute glomerulonephritis due tostreptococcihave elevated levels of ASO.

Autoimmune & Inflammation

Assists in the diagnosis of thyroid diseases such as endemic goiter, Graves Disease, autoimmune thyroiditis, Addison's Disease, insulin-dependent diabetes mellitus, Hashimoto's Disease and polyendocrine auto-immunopathies.

Autoimmune & Inflammation

Offered as part of multiple lab tests

Autoimmune & Inflammation

Serum lysozyme has been proposed as a parameter for monitoring disease progression/regression in cases of proven sarcoidosis.2Revised FAB (French, American, British) criteria indicate that serum or urine lysozyme levels 3x normal fulfill one of three criteria for the presence of M4/M5 (acute myeloid leukemia with monocytic differentiation) vs M2 (acute myeloblastic leukemia with maturation).Lysozyme, a hydrolytic enzyme and bacteriolytic glycosidase, when present in large amounts may appear as a far cathodal migrating (“cationic”) band on serum or urine protein electrophoresis. Lysozyme has been found in all three human neutrophil granules (azurophil, specific, and gelatinase types).3It is elevated in some cases of myelogenous and in most cases of myelomonocytic and monocytic leukemia. The elevation is proportional to the degree of monocytic differentiation and to tumor cell burden and, if marked, can result in potassium wasting and hypokalemia.4Lysozyme has been found within the granules of normal and leukemic eosinophils by immunoelectron microscopic study. Elevated serum lysozyme may not establish the presence of monocytic differentiation in cases of acute myelogenous leukemia with eosinophilia.5The level of serum lysozyme has been used as a predictor of CNS involvement in these leukemias.6Serum lysozyme has been shown to be elevated in a number of conditions, including tuberculosis and sarcoidosis as well as leukemia.2Sensitivity for prediction of sarcoidosis was 79% in a recent study (compare that of serum angiotensin-converting enzyme (ACE) at 59% in the same study).2The serum lysozyme level increased with the number of organs involved. Serum lysozyme, however, is less specific for sarcoidosis than serum ACE. When utilizing a turbidimetric method for measurement of serum lysozyme activity, there was evidence that such an assay was useful in differentiating infection from rejection in transplant recipients.7

Autoimmune & Inflammation

Offered as part of multiple lab tests

Autoimmune & Inflammation, Infectious Diseases

CH50 is a screening test for total complement activity. Levels of complement may be depressed in genetic deficiency, liver disease, chronic glomerulonephritis, rheumatoid arthritis, hemolytic anemias, graft rejection, systemic lupus erythematosis, acute glomerulonephritis, subacute bacterial endocarditis and cryoglobulinemia. Elevated complement may be found in acute inflammatory conditions, leukemia, Hodgkin's Disease, sarcoma, and Behcet's Disease.

Autoimmune & Inflammation, Infectious Diseases

This test can be useful for the detection of cold agglutinins in association with cold agglutinin syndrome

Autoimmune & Inflammation

Interleukein-6 (IL-6) is a pleiotropic cytokine that acts as both a pro-inflammatory and anti-inflammatory mediator that plays an important role in the proliferation and differentiation of cells in humans.4-7IL-6 is involved in many physiological responses, including acute phase response, fever induction, angiogenesis, B and T cell differentiation as well as in lipid and iron metabolism.8IL-6 is produced locally at the site of infectious or injured lesions and is delivered to the whole body via the blood stream, promptly activating the host defense system to perform diverse functions.6This essential cytokine stimulates acute phase reactions, immune responses, hematopoiesis and various internal organs to prepare for host defense.6IL-6 is an important mediator of fever and the acute phase response that enhances the innate immune system to protect against tissue damage.7In severe cases, IL-6 levels measured can trigger excessive defense signaling and threaten survival.9Sustained and excessive production of IL-6 can occur in a variety of inflammatory diseases.4-7,10Historically. the first disease to be associated with markedly elevated IL-6 was cardiac myxoma, a benign heart tumor, where increased IL-6 levels cause extensive inflammatory symptoms.11,12Markedly elevated IL-6 levels are also found in Castleman's disease, a condition where patients suffer from severe inflammatory symptoms related to massive infiltration of mature plasma cells into lymph nodes.13IL-6 is involved in pathogenesis of rheumatoid arthritis14,15and other autoimmune conditions.5Elevated levels of IL-6 in patients with community acquired pneumonia are associated with increased all-cause and cause-specific mortality during admission and over one-year post-admission, despite resolution of clinical signs of an acute infection.16-18Increased amounts of IL-6 in serum were associated with pulmonary inflammation and extensive lung in SARS coronavirus patients.19,20Secondary haemophagocytic lymphohistiocytosis (sHLH) is a hyperinflammatory syndrome characterized by a massive and often fatal increase in cytokine levels (including IL-6) with multi-organ failure that is most commonly triggered by viral infections.21-22A cytokine release syndrome (CRS), similar to sHLH, with markedly increased levels of a number of cytokines including IL-6 has been reported in patients with severe COVID-19 infections.15,23-32IL-6 levels have been found to be more elevated patients with severe COVID-19 as compared to non-severe cases26and IL-6 has been reported to be a clinical predictor of mortality in these patients.25,28Many patients with confirmed COVID-19 have developed fever and/or symptoms of severe inflammatory responses, sometimes referred to as "cytokine release syndrome"(CRS) or "cytokine storm."2Severe symptoms may occur in >20% of COVID-19 patients. Symptoms of severe inflammatory response in COVID-19 may include, but are not limited to, fever, hypotension. dyspnea, organ dysfunction, and organ failure.2Among the different cytokines that may contribute to systemic inflammation, measurement of IL-6 can be indicative of the severity of such inflammation because IL-6 is known to have a central role in inflammation.2Measurement of IL-6 in COVID-19 confirmed patients is used to identify patients with severe inflammatory response who may be at risk of intubation with mechanical ventilation.2Healthcare professionals may use the IL-6 measurement together with other laboratory and clinical findings. Elevated IL-6 levels may be an important indicator of severe inflammatory response.1,2In an external study using Elecsys IL-6 on samples from 817 apparently healthy individuals, the upper limit of the reference range for IL-6 was 7 pg/mL (95th percentile).1-2The following clinical data are from Munich, Germany, from polymerase chain reaction (PCR) confirmed symptomatic COVID patients presenting in the Emergency Department (ED). In the validation data set of 49 hospitalized patients, 19 patients required intubation for respiratory support subsequent to ED presentation.1,32The Elecsys IL-6 assay, using a cutoff of 35 pg/mL, correctly identified 16 of the 19 patients that required intubation — positive predictive value: 59% (95% Cl = 47% to 71%); negative predictive value: 86% (95% Cl = 68% to 95%); prevalence of mechanical ventilation in COVID-19 confirmed, hospitalized patients: 39% (95% Cl = 25% to 54%).3The cutoff was established on retrospectively collected samples (n=37) and validated with prospectively collected samples (n=49) based on the need for mechanical ventilation during the hospitalization. The receiver operator curve was calculated for the first assessment value of Elecsys IL-6 at presentation to the ED. Sensitivity and specificity is shown for patients who subsequently underwent or did not undergo intubation with mechanical ventilation.

Autoimmune & Inflammation

Offered as part of multiple lab tests

Autoimmune & Inflammation

Tissue Transglutaminase Antibody, IgG, is useful in diagnosing gluten-sensitive enteropathies, such as Celiac Sprue Disease, and an associated skin condition, dermatitis herpetiformis in patients who are IgA-deficient.

Autoimmune & Inflammation

Offered as part of multiple lab tests

Autoimmune & Inflammation

The DAT (Direct Coomb's test) is positive if red cells have been coated, in vivo, with immunoglobulin, complement, or both. A positive result can occur in immune-mediated red cell destruction, autoimmune hemolytic anemia, a transfusion reaction or in patients receiving certain drugs.

Autoimmune & Inflammation, Bone Health

A synthetic circular peptide containing citrulline called CCP IgG (cyclic citrullinated peptide) has been found to be better at discriminating Rheumatoid Arthritis patients from patients with other diseases such as hepatitis C infection. Rheumatoid Arthritis Classification Criteria include CCP IgG Antibody, rheumatoid factor, C-reactive protein and erythrocyte sedimentation rate (ESR). Approximately 70% of patients with Rheumatoid Arthritis are positive for Anti-CCP IgG, while only about 2% of random blood donors and disease controls subjects are positive.

Autoimmune & Inflammation

The C1 esterase inhibitor protein is a normal constituent of serum which functions as a serine proteinase inhibitor of the serpin family. The C1 esterase inhibitor inhibits the complement proteases C1r and C1s, as well as the proteases Kallikrein, factor XIa, XIIa and plasmin of the blood clotting system. The concentration of C1 esterase inhibitor protein is reduced to 10-30% of normal in patients with angioedema secondary to C1 esterase inhibitor deficiency (85% of patients with hereditary angioedema (HAE)); in 15% of patients with HAE, the concentrations of the inhibitor protein is normal but function is markedly reduced.

Autoimmune & Inflammation

Anti-centromere abs are found in 46% of patients with Limited Systemic Sclerosis and 11% in Diffuse Systemic Sclerosis, as well as 12% of patients with primary biliary cirrhosis, and are rarely present in normal individuals. The antibodies are associated with CREST syndrome.

Autoimmune & Inflammation

Sjögren's antibodies (SS-B) is detected in approximately 15% of patients with Sjögren's Syndrome. Sjögren's antibody (SS-B) is present only if Sjögren's antibody (SS-A) is also detected. The presence of both antibodies (SS-A and SS-B) strengthen the diagnosis of Sjögren's Syndrome and conveys prognostic information.

Autoimmune & Inflammation

Offered as part of multiple lab tests

Autoimmune & Inflammation, Liver & Kidney Health

The presence of LKM-1 antibodies can be used in conjunction with clinical findings and other laboratory tests to aid in the diagnosis of autoimmune liver diseases such as autoimmune hepatitis (AIH-2).

Autoimmune & Inflammation, Digestive Health

Gastric Parietal Cell Antibodies are found in 90% of patients with pernicious anemia. They are also found in autoimmune chronic atrophic gastritis preceding pernicious anemia. The antigenic target is the H+/K+ ATPase gastric proton pump responsible for parietal cell acid generation in the stomach.

Autoimmune & Inflammation

Offered as part of multiple lab tests

Digestive Health, Autoimmune & Inflammation

Calprotectin is a non-specific marker of bowel inflammation. Subsequent to white blood cell migration into the intestine, this neutrophil protein may be detected in the stool. Thus, fecal calprotectin levels may assist in diagnosis of inflammatory bowel disease; Crohn's disease and ulcerative colitis and other disorders characterized by bowel inflammation. It can also be used as an aid in the differentiation of IBD from irritable bowel syndrome.

Autoimmune & Inflammation

Offered as part of multiple lab tests

Digestive Health, Autoimmune & Inflammation

Offered as part of multiple lab tests

Diabetes & Blood Sugar, Autoimmune & Inflammation

Type 1 diabetes, commonly referred to as insulin-dependent diabetes (IDDM), is caused by pancreatic beta-cell destruction that leads to an absolute insulin deficiency.1The clinical onset of diabetes does not occur until 80% to 90% of these cells have been destroyed. Prior to clinical onset, type 1 diabetes is often characterized by circulating autoantibodies against a variety of islet cell antigens, including glutamic acid decarboxylase (GAD), tyrosine phosphatase (IA2), and insulin.2-5The autoimmune destruction of the insulin-producing pancreatic beta cells is thought to be the primary cause of type 1 diabetes. The presence of these autoantibodies provides early evidence of autoimmune disease activity, and their measurement can be useful in assisting the physician with the prediction, diagnosis, and management of patients with diabetes. Insulin is the only beta-cell specific autoantigen thus far identified.4-6Antibodies to insulin are found predominantly, though not exclusively, in young children developing type 1 diabetes. In insulin-naive (untreated) patients, the prevalence of antibodies to insulin is almost 100% in very young individuals and almost absent in adult onset of type 1 diabetes. Because the risk of diabetes is increased with the presence of each additional autoantibody marker, the positive predictive value of insulin antibody measurement is increased when measured in conjunction with antibodies to GAD and IA-2.2-4

Autoimmune & Inflammation

SeeComplement C1 Esterase Inhibitor [004648].

Autoimmune & Inflammation

Offered as part of multiple lab tests

Autoimmune & Inflammation

Anti-Jo-1 antibodies are present in approximately 20% to 30% of patients with adult-onset polymyositis syndromes. They are present in >65% of patients with both myositis and interstitial lung disease. In such patients, the presence of anti-Jo-1 antibodies may be predictive of a response to steroid treatment. Testing for ANAs is not adequate for the detection of anti-Jo-1 antibodies.

Autoimmune & Inflammation

Offered as part of multiple lab tests

Autoimmune & Inflammation

Chronic urticaria is a common skin disorder affecting 1 to 6% of the general population. It is characterized by repeated occurrence of short-lived cutaneous wheals accompanied by redness and itching. Autoimmune urticaria is defined by the presence of a functional IgG antibody to high-affinity IgE receptor (Fc epsilon RI alpha) or to IgE. These antibodies trigger mast cell and basophil degranulation by the engagement of Fc epsilon receptor. Functional IgG antibody to the receptor has been identified in approximately 30-40% of patients with chronic urticaria, and anti-IgE antibody has been identified in another 5% to 10%. The anti-IgE assay will quantify autoantibodies to IgE which will aid in the diagnosis and management of autoimmune chronic urticaria.

Autoimmune & Inflammation

Adrenal Antibody is detected in patients with autoimmune adrenal disease, e.g., Addison's disease.

Autoimmune & Inflammation, Infectious Diseases

Lysozyme in the serum is primarily due to the degradation of granulocytes and monocytes and its concentration reflects the turnover of these cells. Increases are seen in benign and malignant processes. Serum lysozyme is elevated in patients with acute or chronic granulocytic or monocytic leukemias and levels decrease with successful treatment. Conversely, patients with lymphocytic leukemia may have depressed plasma lysozyme levels.

Autoimmune & Inflammation

Detection of antibodies to gliadin, one of the major protein components of gluten, is a sensitive assay useful in diagnosing celiac disease. However, gliadin antibodies may be found in individuals without celiac disease; thus gliadin antibody assays are less specific than assays measuring antibodies to endomysium and transglutaminase. Recent work has revealed that gliadin-reactive antibodies from celiac patients bind to a very limited number of specific epitopes on the gliadin molecule. Further, deamidation of gliadin results in enhanced binding of gliadin antibodies. Based on this information, assays using deamidated gliadin peptides bearing the celiac-specific epitopes have much higher diagnostic accuracy for celiac disease when compared to standard gliadin antibody assays.

Autoimmune & Inflammation

Jo-1 Antibody occurs most frequently (31%) in patients with polymyositis, but has also been found in patients with dermatomyositis, and the polymyositis/scleroderma "overlap syndrome" (PM/SCL) or polymyositis/systemic lupus erythematosis "overlap syndrome" (PM/SLE).

Infectious Diseases, Autoimmune & Inflammation

Documents recentstreptococcalinfection.

Autoimmune & Inflammation

Cytokines are low-molecular-weight intercellular signaling molecules.1-4Cytokines are produced de novo in response to an immune stimulus. They regulate immune cell homeostasis by mediating innate and acquired immunity, and inflammation in human health and disease. They generally (although not always) act over short distances and short time spans and at very low concentrations. They act by binding to specific membrane receptors, which then signal the cell via second messengers, often tyrosine kinases, to alter its behavior. Responses to cytokines include increasing or decreasing expression of membrane proteins (including cytokine receptors), proliferation and secretion of effector molecules. It is common for different cell types to secrete the same cytokine or for a single cytokine to act on several different cell types (pleiotropy). Cytokines are redundant in their activity, meaning similar functions can be stimulated by different cytokines. Cytokines are often produced in a cascade, as one cytokine stimulates its target cells to make additional cytokines. Cytokines can also act synergistically (two or more cytokines acting together) or antagonistically (cytokines causing opposing activities).Tumor necrosis factor-alpha (TNF-α) is an important pleiotropic cytokine involved in host defense, inflammation, and apoptosis.3Local increases in TNF-α concentrations cause the five cardinal signs of inflammation: heat, swelling, redness, pain and loss of function.3TNF-α was initially identified as a serum factor that could induce the hemorrhagic necrosis of tumors in patients following acute bacterial infections.5TNF-α is a central cytokine in inflammatory reactions, and biologics that neutralize TNF are among the most successful drugs for the treatment of chronic inflammatory and autoimmune pathologies.5In recent years, it became clear that TNF-α drives inflammatory responses not only directly by inducing inflammatory gene expression but also indirectly by inducing cell death, instigating inflammatory immune reactions and disease development.5It plays a double role in regulation of immune responses, acting both as a proinflammatory mediator, initiating a strong inflammatory response, and an immunosuppressive mediator, inhibiting the development of autoimmune diseases and tumorigenesis, and exhibiting a vital role in maintenance of immune homeostasis by limiting the extent and duration of inflammatory processes.3TNF-α plays an important role in host defense against viral, bacterial, fungal, and parasitic pathogens, in particular against intracellular bacterial infections, such as Mycobacterium tuberculosis and Listeria monocytogenes.3High systemic TNF-α levels can lead to septic shock.3TNF-α has been implicated in the development of allergic diseases, particularly asthma,6and atopic dermatitis.7Serum TNF-α results can be significantly increased in patients with systemic mastocytosis.8The correlation coefficients between highly elevated histamine and cytokine concentrations during the acute phase were >95%, indicating the same cellular origin, possibly activated mast cells.8Elevated TNF-α levels have been associated with worse survival in patients with severe COVID-19 infection.9-11Elevated TNF-α levels have been observed in hospitalized patients with acute lung injury.12

Autoimmune & Inflammation

Offered as part of multiple lab tests

Autoimmune & Inflammation

Smith Antibody (Sm) is highly specific for systemic lupus erythematosus (SLE). Smith Antibody is also detected in approximately 15% of patients with SLE. Smith Antibody is detected in more than half of young African-American women with SLE.

Autoimmune & Inflammation

RNP Antibodies have been associated with Mixed Connective Tissue disease.

Autoimmune & Inflammation, Bone Health

HLA-B27 is found in 90% of patients with ankylosing spondylitis and 80% in Reiter's disease. Ankylosing spondylitis affects 1 in 1000 caucasians. Ankylosing spondylitis is 10 times more common among individuals with HLA-B27 compared to individuals without this antigen.

Autoimmune & Inflammation, Infectious Diseases

This panel separately reports CD4+ T cells (CD4) and CD8+ T cells (CD8) in the blood, as well as a calculated CD4/CD8 ratio. This panel may provide information of the immune status of individuals living with HIV. It can be used to help establish baseline values and track antiretroviral (ARV)-related treatment progress. It can also be used to evaluate helper and suppressor cell immune status in individuals with other immunodeficiency diseases.The CD4 count is the most valuable indicator of immune status in HIV-infected individuals. It can help determine the need for prophylaxis for opportunistic infections and the urgency of ARV initiation. The CD8 count reflects the level of immune activation in response to HIV. In the early stages of infection, CD4 levels and the CD4/CD8 ratio typically decline after seroconversion occurs. However, after seroconversion, CD8 cells increase in an attempt to mount a response against HIV. In ARV-treated patients with controlled viral load, CD8 counts. Post-therapy, persistently elevated CD8 counts have been linked to increased risk of non--AIDS-defining diseases, independent of CD4 count, including cardiovascular, renal, respiratory, metabolic diseases, and cancer [1-3].This panel can be used to establish baseline CD4 and CD8 levels, as well as percentages and ratios, which help determine how long the virus has been present in the blood and the overall prognosis. During ARV treatment, this panel can help assess CD4 recovery and CD8 response to treatment [1,2].During the first 2 years of ARV therapy, The National Institutes of Health recommends testing CD4 every 3 to 6 months. Patients who develop viremia while on therapy or whose CD4 count stays below 300 cells/µL. should also have their CD4 levels tested every 3 to 6 months. After 2 years of ARV therapy, with consistently suppressed viral load and a CD4 count of 300 to 500 cells/µL, CD4 counts should be tested every 12 months. CD4 testing should also be conducted if therapy fails. Note that CD4 testing is optional when CD4 counts are >500 cells/µL [1].References1. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services.https://aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf. Updated July 10, 2019. Accessed November 10, 2019.2. Warren JA, et al.Front Immunol. 2019;10:291. Published February 26, 2019. doi:10.3389/fimmu.2019.002913. Cao W, et al.J Int AIDS Soc. 2016;19:20697. Published March 3, 2016. doi: 10.7448/IAS.19.1.20697

Autoimmune & Inflammation

Centromere B Antibody is diagnostic for the form of scleroderma known as CREST (calcinosis, Raynaud's phenomenon, esophageal immotility, sclerodactyly, and telangiectasia).

Autoimmune & Inflammation

Individuals with the antiphospholipid antibody syndrome (APS) have an increased risk for stroke, myocardial infarction, venous thrombosis, thromboembolism, thrombocytopenia, and/or recurrent miscarriages. In 1999, an international consensus conference found that one criterion for the serologic diagnosis of “definite antiphospholipid syndrome” is the presence of anticardiolipin antibody of IgG and/or IgM isotype, at medium or high titer, on two or more occasions, at least six weeks apart.3The presence of ACA of moderate to high titer for IgG is strongly associated with both arterial and venous thrombosis and recurrent pregnancy loss.1,4,5The IgM isotype of ACA has also been shown to be associated with venous thrombosis.4Other studies found that ACA of the IgA isotype at moderate to high titer can also be associated with increased risk of APS.2,6ACA antibodies are quite common in the general population and are not always associated with APS. Studies indicate that there is a higher prevalence of IgM positives than IgG in the general population with these isotypes occurring in 9.4% and 6.5% of the population, respectively.7The incidence of these ACA is even higher in normal pregnancy with detection rates of 17% for IgM and 10.6% for IgG.8Many of these antibodies are transient and not associated with APS. The diagnosis of APS should not be made on the basis of a single ACA result but rather on repeated positive results obtained at least six weeks apart.2The Venereal Disease Research Laboratory (VDRL) agglutination test that has been used for decades in the diagnosis of syphilis is based on the detection of antibodies to cardiolipin.9The first solid-phase immunoassays for ACA were developed in the early 1980s.9These solid-phase assays are at least 100-fold more sensitive than the classical VDRL assay and produce many more positive results. In general, ACA are considered to be more sensitive than lupus anticoagulants (LA) for the detection of APS.4The ACA test is positive in 80% to 90% of patients with APS,10and ACA are implicated in approximately five times more cases of APS than are LA;1however, LA are considered to be more specific for APS than ACA.1,10Due to the heterogeneity of antibodies associated with APS, both LA and ACA testing is recommend when APS is suspected.4,11ACA are frequently observed in patients with other autoimmune disorders and malignancies. Individuals with ACA secondary to these other conditions are at increased risk of developing APS. A variety of therapeutic drugs can induce the production of ACA. These drug-induced antibodies may be clinically significant if they persist.2,12

Autoimmune & Inflammation

Results may indicate malabsorption or maldigestion. False positive results can occur due to mineral oil or castor oil present in the specimen. Large number of neutral fat globules may indicate steatorrhea.

Autoimmune & Inflammation

Cardiolipin antibodies (CA) are seen in a subgroup of patients with autoimmune disorders, particularly systemic lupus erythematosus (SLE), who are at risk for vascular thrombosis, thrombocytopenia, cerebral infarct and/or recurrent spontaneous abortion. Elevations of CA associated with increased risk have also been seen in idiopathic thrombocytopenic purpura, rheumatoid and psoriatic arthritis, and primary Sjögren's syndrome.

Diabetes & Blood Sugar, Autoimmune & Inflammation

Offered as part of multiple lab tests

Diabetes & Blood Sugar, Autoimmune & Inflammation

Offered as part of multiple lab tests

Digestive Health, Autoimmune & Inflammation

Gluten is a protein found in wheat, rye and barley. Gliadin is the alcohol-soluble fraction of gluten that contains the bulk of the toxic components of gluten. It is resistant to degradation in the human upper gastrointestinal tract and is able to pass through the epithelial barrier of the intestine. Gluten sensitivity is a state of heightened immunological responsiveness to ingested gluten. It represents the spectrum of diseases with diverse manifestations such as enteropathy (celiac disease), dermatopathy (dermatitis herpetiformis), neurological disorders (ataxia and neuropathy), and may be underlying reason for many other nonspecific symptoms like anemia, chronic fatigue, joint inflammation and pain, migraines, depression, attention-deficit disorder, epilepsy, osteoporosis and osteopenia, infertility, recurrent fetal loss, vitamin deficiencies, short stature, failure to thrive, delayed puberty, dental enamel defects, and autoimmune disorders. Patients with gluten sensitivity are reported to have increased mortality and its prevalence in the general population is up to 12%.Antibodies to deamidated gliadin peptide and tissue transglutaminase are specific to celiac disease while antibodies to native gliadin are present in patients with and without gastrointestinal manifestations and are serological evidence of gluten sensitivity. Another subset of patients may have gluten sensitivity expressed in the form of allergic reaction to foods containing gluten like wheat. All of those patient groups may benefit from gluten-free diet.This screening profile is designed to aid in the diagnosis of different forms of gluten sensitivity.Step One:The screening starts with testing for tTG IgA and DGP IgG.1,2When any or both of the results are positive, testing stops and the interpretive comment on the report would read: "Suggestive of celiac disease or other gluten-sensitive enteropathies. Subsequent testing forEndomysial Antibody, IgA [164996]and/or genetic testing forCeliac Disease HLA DQ Association [167082]may be indicated for further patient evaluation." When result is negative, testing will reflex to the second step.Step Two:In the second step, the test for IgG antibodies to native gliadin (AGA) is performed. AGA currently remain the most sensitive markers of the whole spectrum of gluten sensitivity including all the extraintestinal manifestations.1,3When the result is positive, testing stops and the interpretive comment would read: "Suggestive of nonceliac gluten sensitivity. The patient may benefit from a gluten-free diet." When the result is negative, testing will reflex to the third step.Step Three:In the third and last step, the test for wheat allergen-specific IgE is performed. Allergic reaction to wheat may mimic the clinical presentation of gluten sensitivity like celiac disease and is one of the common food allergies in children. The triggering agent, however, may not be just gluten but any other protein or combination of proteins found in wheat.4Because wheat allergy patients may also be allergic to other grains with similar proteins like rye and barley,4they will benefit from the gluten-free diet. When the result is positive, testing stops and the interpretive comment would read: "Suggestive of wheat allergy. The patient may benefit from a gluten-free diet." When the result is negative, testing stops and the interpretive comment would read: “Not suggestive of gluten sensitivity.”

Autoimmune & Inflammation

Antibodies that produce a speckled ANA pattern are usually directed against extractable nucleoprotein complexes found in the nucleus and/or cytoplasm of substrate cells. Included in this group of antigens are RNP, Sm, SS-A, SS-B, Scl-70, and Jo-1.

Autoimmune & Inflammation

Graves' disease (GD) is an autoimmune disorder and the most common cause of hyperthyroidism.2-7In GD, thyroid stimulating immunoglobulins (TSI) bind to the TSH receptor (TSHR) and mimic TSH stimulation of the thyroid gland. Because TSI induced thyroid hormone secretion is not controlled by negative feedback, such stimulation causes uncontrolled hyperthyroidism.8Extrathyroidal manifestations of GD include endocrine exophthalmos, pretibial myxedema. GD is characterized thyroid acropachy, i.e., the soft-tissue swelling of the hands and clubbing of the fingers. Radiographic imaging of affected extremities typically demonstrates periostitis, most commonly the metacarpal bones. TSI are IgG antibodies that can cross the placental barrier and cause neonatal thyrotoxicosis in newborns delivered by mothers with GD.9,10The TSH receptor contains a large extracellular domain that presents epitopes for a variety of autoantibodies, including TSI and Thyroid Blocking Immunoglobulins TBI.11-13In contrast to TSI, TBI bind to the TSH receptor and inhibit TSH stimulation of thyroid cells, leading to hypothyroidism. Commonly used Thyrotropin Receptor Autoantibody (TRAb) assays do not distinguish between TSI and TBI. The IMMULITE 2000 TSI assay utilizes recombinant human TSH receptors (hTSHR) for the specific detection of thyroid stimulating autoantibodies.1The clinical utility of TSI measurement includes a determination of the autoimmune etiology of thyrotoxicosis,2-7monitoring GD patient therapy,14prediction of remission or relapse,15confirmation of Graves' ophthalmopathy,16and prediction of hyperthyroidism in neonates.9,17,18TheTSI test is used for the differential, diagnosis of etiology of thyrotoxicosis in patients with ambiguous clinical signs or indeterminate thyroid radioisotope scans.3TSI can also be of value in determining the risk of neonatal thyrotoxicosis in a fetus of a pregnant female with active or past GD and the differential diagnosis of gestational thyrotoxicosis versus first-trimester manifestation or recurrence of GD.9,10TSI can also be ordered to assess the risk of GD relapse after antithyroid drug treatment.Several published studies have evaluated the sensitivity and specificity of the Siemens TSI assay for diagnosing GD patients and discriminating them from patients with other thyroid diseases.19-22Kembel and coworkers23evaluated three commercially available anti-TSHR autoantibody measurement methods and found equivalent performance in patients with untreated GD. However, discordant results were observed when testing specimens collected from patients undergoing treatment for GD. In these patients, the Siemen TSI assay more frequently generated results consistent with clinical history, results of other laboratory tests, and imaging studies than the TSI bioassay and Roche TRAb assay. In the validation for FDA submission,11serum samples from 361 treated and untreated hyperthyroid Graves' disease patients, and 404 individuals with other thyroid or autoimmune diseases were evaluated. The TSI values for patients without GD with other thyroid or autoimmune diseases had an upper limit of 0.39 IU/L. At the 0.55 IU/L cut-off, the clinical sensitivity and specificity for GD were 98.6% and 98.5%, respectively.

Autoimmune & Inflammation

Graves' disease is a classic form of hyperthyroid disease, affecting approximately 0.4% of the population of the United States. It is caused by IgG immunoglobulins, collectively known as thyroid stimulating immunoglobulins (TSI). Patients who are candidates for antithyroid drug therapy may not respond to this treatment when TSI levels are markedly elevated. The determination of TSI can also assist in predicting hyperthyroidism in neonates, due to placental transmission of the immunoglobulins from a mother with hyperthyroidism.

Autoimmune & Inflammation, Heart Health & Cardiovascular

Autoimmune vasculitis diseases are characterized by abnormal immune responses that result in inflammation and necrosis of blood vessels. The immune dysfunction may be triggered by infection, autoimmune disease, or exposure to a drug; often the cause is unknown. ANCA-associated vasculitis diseases are often characterized by the size of the blood vessels involved. The diseases present with diverse clinical features and are often rapidly progressive, causing irreversible injury to the vessels of the organs affected, such as the kidneys and lungs.

Autoimmune & Inflammation

Iodine is as essential element that is required for thyroid hormone production. The measurement of urinary iodine serves as an index of adequate intake.

Autoimmune & Inflammation

Smith (Sm)/U1-RNP Antibody is detected in patients with mixed connective tissue disease (having features of systemic lupus erythematosus (SLE), scleroderma, and polymyositis).

Autoimmune & Inflammation

Offered as part of multiple lab tests

Autoimmune & Inflammation

Scl-70 antibody is seen in 20% of patients with scleroderma, and in some patients with CREST syndrome (calcinosis, Raynaud, esophageal dysfunction, sclerodactyly, telangiectasia). These syndromes are also associated with a high frequency of speckled pattern immunofluorescent antinuclear antibody tests. Scl-70 may identify a subset of scleroderma patients with severe skin, joint, and lung disease. In addition, the presence of Scl-70 in Raynaud phenomenon may indicate a poor prognosis.

Autoimmune & Inflammation

Chromatin Antibody plays a central role in the autoimmune response in systemic lupus erythematosus (SLE). Approximately 90% of patients with SLE have sera that will exhibit reactivity to nucleosomes.

Autoimmune & Inflammation

Scl-70 antibody is present in approximately 40% of patients with progressive systemic sclerosis (PSS).

Autoimmune & Inflammation

Measurement of TRAb is used to diagnose and manage Graves' disease, neonatal hypothyroidism, and postpartum thyroid dysfunction. TRAb, which measures the ability of antibodies to inhibit TSH binding to its receptor, reflects the presence of either or both the stimulatory and inhibitory immunoglobulin classes.

Autoimmune & Inflammation, Heart Health & Cardiovascular

Cardiolipin antibodies (CA) are detected in a subgroup of patients with autoimmune disorders, particularly Systemic Lupus Erythematosus (SLE), who are at risk for vascular thrombosis, thrombocytopenia, cerebral infarct and/or recurrent spontaneous abortion. Elevations of CA associated with increased risk have also been seen in idiopathic thrombocytopenic purpura, rheumatoid and psoriatic arthritis, and primary Sjögren's syndrome.

Autoimmune & Inflammation

Various types of organic disease in the gastrointestinal tract will cause damage to the intestinal lining (mucosa layer). Such damage may vary from increased permeability of the mucosa to inflammation, which may be toxic or chemotactic (ie, they stimulate leukocytes, in particular polymorphonuclear granulocytes [PMNs] to migrate into the gut lumen where they release their contents, including antimicrobial substances like calprotectin). This protein constitutes about 60% of total proteins in the cytoplasm of PMN and can be estimated in small, random stool samples even after storage for seven days at ambient temperature. The concentration of calprotectin in stool reflects the number of PMNs migrating into the gut lumen.Calprotectin is a calcium- and zinc-binding protein produced by PMNs, monocytes, and squamous epithelial cells, except those in normal skin. After binding calcium, it can resist degradation by leukocytic and bacterial enzymes. By competing with different enzymes for limited local amounts of zinc, calprotectin may inhibit many zinc-dependent enzymes and thereby kill microörganism or animal and human cells in culture.Calprotectin can be detected even in small (<1 g) random stool samples. Furthermore, organic diseases of the bowel give a strong fecal calprotectin signal (ie, elevations are often five to several thousand times the upper reference in healthy individuals indicating intestinal inflammation). Patients with organic or functional abdominal disorders may have similar symptoms, and clinical examination alone may not be sufficient to support a specific diagnosis. Additionally, the calprotectin test has been demonstrated to be a marker of inflammatory bowel disease in both children and adult patients.Inflammatory bowel disease (IBD) (eg, ulcerative colitis and Crohn's disease), may appear from early childhood to late adulthood, and the diagnosis is often delayed due to vague symptoms or reluctance to perform endoscopy and biopsy.

Autoimmune & Inflammation, Infectious Diseases

C3a desArg is a cleavage product of C3 complement component activation. Elevated levels of C3a have been reported in patients with acute lyme disease, acute pancreatitis, systemic lupus erythematosus, and adult respiratory distress syndrome.

Autoimmune & Inflammation

The complement system is an ancient and highly conserved effector mechanism of the innate immune system with important functions in immune defense.4-9The main outcomes of complement system action are lytic killing of microbes, the rapid clearance of pathogens and dead or dying cells and immune complexes, and the release of pro-inflammatory anaphylatoxins. Activation and amplification of complement leads to destruction of pathogens or abnormal host cells through opsonization – a process by which complement ligands coat surfaces, targeting them for phagocytosis – or by lysis induced upon formation of the membrane attack complex (MAC), also referred to as the terminal complement complex (TCC). The ability to differentiate between self and non-self (or damaged/altered self) is a hallmark feature of the complement system. As a general paradigm, this is accomplished through complement recognition of components unique to microbial entities, often consisting of specific carbohydrate structures that are not found on host surfaces that are referred to as pathogen-associated molecular patterns (PAMPs).10,11Similarly, activated complement proteins are also able to recognize abnormal glycosylation patterns on the surface of dead or dying host cells (termed damage-associated molecular patterns, or DAMPs) and immune complexes, activating complement mechanisms that lead to their clearance. Complement activation also works to link innate and adaptive immune reactions by mediating T cell and B cell responses. The complement pathway is tightly regulated to avoid uncontrolled activation.12,13C3, the central component of the complement system, is present in the blood in concentrations of more than 1 mg/mL, which makes it one of the most represented proteins in circulation.14,15Native C3is biologically inactive, but its activation fragments have a multitude of biological functions. Complement activation can occur through three separate mechanisms: the classical pathway, the lectin pathway and the alternate pathway, each of which is activated by different molecules.16In the first pathway to be discovered, the classical pathway, C3is activated by antigen-antibody complexes that bind complement C1q.7-9The lectin pathway is initiated by pathogen-associated molecular patterns (PAMPs), small molecular motifs, that are characteristic of microbial pathogens and are not present on mammalian tissues. These include mannose-binding lectin (MBL) and numerous other carbohydrate structures. The alternate pathway is continuously activated at a low level as a result of spontaneous C3hydrolysis allowing for activation on surfaces that lack proper complement regulation, typically non-host surfaces.12,14,17All complement activation pathways converge at the point of C3cleavage, which results in generation of bioactive fragments including C3b and C3a.18C3b is an efficient opsonin that marks foreign structures for phagocytosis; C3b also forms a membrane complex with other complement proteins to activate complement C5, yielding C5a and C5b. Like the C3a generated in the proximal portion of the cascade, C5a serves as an anaphylatoxin, a substance released into surrounding fluids and tissues to recruit/activate inflammatory cells. C5b triggers assembly of the membrane attack complex (MAC), also referred to as the terminal complement complex (TCC), a pore-forming structure made up of C5, C6, C7, C8and multiple C9molecules. The MAC forms a channel once inserted into the lipid bilayer, leading to lysis of cells or infecting organisms.C3a is the only bioactive fluid phase fragment generated by C3cleavage.14C3a is referred to as anaphylatoxins because it causes smooth muscle contraction, vasodilation, histamine release from mast cells and enhanced vascular permeability.5-7,19,20C3a is a potent chemoattractant that recruits several types of phagocytes to the site of inflammation and triggers the production of reactive oxygen species in macrophages, eosinophils and neutrophils. C3a exerts bactericidal activity by binding to their membranes and inducing cell lysis.21C3a can act on neutrophils to prevent their mobilization from the bone marrow to the circulation after ischemia-reperfusion injury.22C3a supports tissue regeneration after liver injury by stimulating cell proliferation, and it contributes to hematopoietic stem cell retention in the bone marrow, homing and engraftment.23-25In the brain, the C3a has an important role in the recovery after the acute phase of ischemic injury, modulating neurogenesis and axonal and synaptic plasticity.26Measurement of plasma C3a levels has been used in the assessment of the extent of complement activation in a variety of clinical conditions.27-29Excessive complement activation can contribute to the pathogenesis of many acute and chronic inflammatory diseases. C3has been implicated in several autoimmune19,30and inflammatory diseases, including acute kidney inflammation,31neurotrauma, anti-phospholipid thrombosis,32asthma and allogeneic transplantation.19,33In susceptible individuals, allergen exposure triggers the activation of complement, leading to the aberrant generation of the C3a anaphylatoxin.20,34-36C3a has been shown to be important for the development of Th2 responses by driving ILC2-mediated inflammation in response to allergen.37C3a binds to receptors on mast cells to trigger the release of histamine and chemokines.9,38Nakano and coworkers found that plasma C3a concentrations were significantly higher in patients seeking emergency treatment for severe asthma exacerbations than in control subjects with stable asthma.39They found that C3a concentrations were highest among patients who failed to improve with treatment with inhaled bronchodilators and intravenous corticosteroids.39They also observed that levels of plasma C3a in admitted asthmatic patients decreased significantly within a week after admission.39Clinical consequences of an overactivated and dysregulated complement system include not only immune complex and autoimmune disorders, such as systemic lupus erythematosus,12,27,40various forms of nephropathy, like atypical hemolytic uremic syndrome,27,41and C3glomerulopathy,27,42,43ophthalmic disorders, like age-related macular degeneration,44but also organ failure subsequent to ischemia reperfusion injury.45Paroxysmal nocturnal hemoglobinuria is an acquired clonal hematopoietic stem cell disorder in which uncontrolled complement activity leads to systemic complications, principally through intravascular hemolysis and thrombosis.27,46C3a have been reported to be significantly higher in rheumatoid arthritis subjects compared to control subjects.47Plasma levels of complement C3a measured daily during the first week after onset of symptoms of acute pancreatitis represent highly specific and sensitive parameters for the prediction of severe acute pancreatitis.48,49Preclinical studies into the mechanism of hepatic regeneration have demonstrated an essential role for C3a in priming the hepatocyte proliferative response after injury or resection.50C3a has also been implicated in the regeneration of bone, cardiac muscle and skeletal muscle, as well as stem cell engraftment.51-53C3a has been used as a marker of neurodegenerative disease.54C3a elevated in plasma one to 14 days after stroke and correlated with prognosis.55-57C3a elevated in serum immediately after traumatic brain injury and remains chronically elevated.58C3a levels have been shown to correlate with disease severity in patients with COVID-1959and in patients with septic shock.60In cancer, C3a can have pro-tumor effects impacting immune system activation at the tumor site and favoring tumor progression. C3a binding to its receptor maintains an immunosuppressive environment in sarcoma and promotes tumor progression by skewing the phenotype of tumor-associated macrophages61while in lung cancer, C3a signaling acts on CD4+ T cells and induces an inhibitory phenotype.62In pancreatic ductal adenocarcinoma, C3a activates the extracellular-regulated kinase pathway, inducing an epithelial-to-mesenchymal transition.63,64In plasma, C3a is quickly converted by carboxypeptidase N into C3a-desArg by cleavage of the C-terminal arginine.65-67C3a-desArg does not bind to the human C3a receptor.68A number of studies have shown that there is a positive relationship between C3a-desArg levels, adipose tissue and risk factors for cardiovascular disease, metabolic syndrome and diabetes.69,70C3a-desArg, also known as acylation stimulation factor, has been purported to play a role in transporting fatty acids to adipocytes and triacylglycerol synthesis.71It has been suggested that production of C3a (and C5a) in adipose tissue triggers a cytokine and chemokine response in proportion to the amount of adipose tissue present and induces inflammation and mediate metabolic effects such as insulin resistance. These observations support the concept that complement activation may be an important participant in lipid metabolism and in obesity, contributing to the metabolic syndrome and to the low-grade inflammation associated with obesity.

Autoimmune & Inflammation, Cancer Screening

To evaluate the level of IL-6 in serum samples.

Autoimmune & Inflammation

Offered as part of multiple lab tests

Autoimmune & Inflammation, Cancer Screening

Test is for research use only, and is for use in patients previously diagnosed with T-cell lymphoma.

Autoimmune & Inflammation

Myasthenia Gravis (MG) is an autoimmune neuromuscular disorder characterized by muscle weakness, most commonly due to autoantibody-mediated loss of functional acetylcholine receptors (AChR) in the neuromuscular junction. AChR binding autoantibodies are diagnostic of MG, and are found in 85-90% of MG patients. This assay aids in the differential diagnosis of conditions with MG-like muscle weakness and in monitoring therapeutic response. If binding antibodies are negative, assays for modulating and blocking antibodies should be considered.

Autoimmune & Inflammation

Antimitochondrial antibodies (AMA) have been reported in 90% to 96% of patients with primary biliary cirrhosis. AMA are also occasionally found in sera of patients with other liver diseases, including chronic active hepatitis, cryptogenic cirrhosis, as well as in patients with clinical but no biochemical evidence of liver disease. The M2 antigen used is strongly associated with PBC, while other types (M1, M2, M5, and M6) are associated with a wide variety of conditions.

Autoimmune & Inflammation

Mitochondrial antibody is present in approximately 95% of patients with Primary Biliary Cirrhosis (PBC). Mitochondrial M2 antibody has an even higher specificity for PBC.

Autoimmune & Inflammation

Offered as part of multiple lab tests

Autoimmune & Inflammation

Histone antibody is present in 80-95% of patients with drug-induced Systemic Lupus Erythematosus (SLE), 20-50% of patients with idiopathic SLE, and infrequently in patients with other autoimmune connective tissue diseases.

Autoimmune & Inflammation, Bone Health

The combination of RF and anti-CCP antibodies provide greater specificity for the diagnosis of Rheumatoid Arthritis (RA). CCP antibodies may be present earlier than RF and often indicate increased erosive disease in RA.

Autoimmune & Inflammation

Offered as part of multiple lab tests

Digestive Health, Autoimmune & Inflammation

Fecal lactoferrin is sensitive and specific for detecting inflammation in chronic IBD. This noninvasive test may be useful in screening for inflammation in patients presenting with abdominal pain and diarrhea.

Autoimmune & Inflammation

Offered as part of multiple lab tests

Autoimmune & Inflammation

Offered as part of multiple lab tests

Autoimmune & Inflammation

There are four subtypes, of which IgG1and IgG2comprise 85% of the total. IgG1and IgG3fix complement best; IgG3is hyperaggregable and effects serum viscosity disproportionately.IgG antibody responses to certain antigens occur to a greater extent in one type of IgG subclass than another. Therefore, some patients with normal total IgG levels may have problems with pyogenic infections because they do not produce IgG2or combinations of IgG2, IgG3, and/or IgG4. Some clinically significant IgG subclass deficiencies occur in patients who have IgA deficiency.The four subclasses of IgG differ in the constant regions of their heavy chains. A patient may have a normal total IgG yet still have a significant decrease in one subclass. IgG1deficiencies are associated with EBV infections, IgG2with sinorespiratory infections and infections with encapsulated bacteria, IgG3with sinusitis and otitis media, and IgG4with allergies, ataxia telangiectasia, and sinorespiratory infections. See tables in individual subclass listings.

Autoimmune & Inflammation

21-Hydroxylase Antibody is present in patients with autoimmune destruction of the adrenal glands, leading to Addison's disease. Antibody is also seen in autoimmune polyglandular syndrome.

Autoimmune & Inflammation

Measurement of IgG subclasses may be helpful in the management and understanding of immunodeficiency diseases, hypersensitivity states, and conditions involving susceptibility to infection.

Diabetes & Blood Sugar, Autoimmune & Inflammation

Type 1 diabetes, commonly referred to as insulin-dependent diabetes (IDDM), is caused by pancreatic beta-cell destruction that leads to an absolute insulin deficiency.1The clinical onset of diabetes does not occur until 80% to 90% of these cells have been destroyed. Prior to clinical onset, type 1 diabetes is often characterized by circulating autoantibodies against a variety of islet cell antigens, including glutamic acid decarboxylase (GAD), tyrosine phosphatase (IA2), and insulin.2-7The autoimmune destruction of the insulin-producing pancreatic beta cells is thought to be the primary cause of type 1 diabetes. The presence of these autoantibodies provides early evidence of autoimmune disease activity, and their measurement can be useful in assisting the physician with the prediction, diagnosis, and management of patients with diabetes. Autoantibodies to IA2, a tyrosine phosphatase-like protein, are found in 50% to 75% of type 1 diabetics at and prior to disease onset. These autoantibodies are generally more prevalent in younger onset patients. Because the risk of diabetes is increased with the presence of each additional autoantibody, the positive predictive value of the IA2antibody test is enhanced when measured in conjunction with antibodies to GAD and insulin.

Autoimmune & Inflammation

Offered as part of multiple lab tests

Autoimmune & Inflammation

This RheumAssure panel is comprised of three tests: RA Factor, CCP Antibodies, and 14-3-3 eta protein.Used together, these three markers are able to diagnose established RA with a sensitivity of 88-96% and early RA with a sensitivity of 78- 92%.1,2RA factor (also called RF) is elevated in established RA (sensitivity 72-85%)2,3and in early RA (sensitivity 44-63%).1,4Its specificity for RA is 80%.3CCP Antibodies have similar sensitivities for established RA (66-79%) and early RA (59%)2,3but higher specificity (90-96%).3,5Serum 14-3-3 eta protein is elevated in both established RA (sensitivity 77%) and early RA (sensitivity 59-64%).1,2It may provide a 15-20% incremental benefit in identifying early RA.1,4Therefore, elevation of one or more markers of RheumAssure is consistent with a diagnosis of rheumatoid arthritis. When all three markers are negative, an RA diagnosis is less likely.

Autoimmune & Inflammation

IgA and IgG antibody testing forS cerevisiaeis useful adjunct testing for differentiating Crohn's disease and ulcerative colitis. Nearly 80% of Crohn's disease patients are positive for either IgA or IgG. In ulcerative colitis, <15% are positive for IgG, and <2% are positive for IgA. Fewer than 5% of healthy controls are positive for either IgG or IgA antibody, and no healthy controls had antibody for both. The atypical ANCA pattern has been observed in a significant percentage of patients with ulcerative colitis, primary sclerosing cholangitis, and autoimmune hepatitis.

Autoimmune & Inflammation

Cytokines are low-molecular-weight intercellular signaling molecules that are produced de novo in response to an immune stimulus.1-3They regulate immune cell homeostasis by mediating innate and acquired immunity, and inflammation in human health and disease. They generally (although not always) act over short distances and short time spans and at very low concentrations. They act by binding to specific membrane receptors, which then signal the cell via second messengers, often tyrosine kinases, to alter its behavior. Responses to cytokines include increasing or decreasing expression of membrane proteins (including cytokine receptors), proliferation and secretion of effector molecules. It is common for different cell types to secrete the same cytokine or for a single cytokine to act on several different cell types pleiotropy). Cytokines are redundant in their activity, meaning similar functions can be stimulated by different cytokines. Cytokines are often produced in a cascade, as one cytokine stimulates its target cells to make additional cytokines. Cytokines can also act synergistically (two or more cytokines acting together) or antagonistically (cytokines causing opposing activities).The cytokine Interleukin-2 (IL-2) exerts crucial functions during immune homeostasis via its effects on regulatory T (Treg) cells, and the optimizing and fine-tuning of effector lymphocyte responses.4IL-2 acts as a growth factor for T cells and serves as a key component of immune activation.5-7Somewhat paradoxically, gene knockout mouse studies have provided evidence that the primary IL-2 function in vivo is the suppression of T responses. Mice lacking IL-2 or its receptor develop lymphadenopathy and T cell-mediated autoimmunity.5,8Interleukin-2 receptor (IL-2R) signaling regulates tolerance and immunity with deficient signaling resulting in autoimmunity.5,9The therapeutic action of IL-2 is related to concentration. Low doses of recombinant IL-2 have been used for Treg cell-based immunosuppressive strategies against immune pathologies, while high-dose IL-2 has shown some success in stimulating antitumor immune responses.4,5The cellular receptor for IL-2 is a three-chain molecule.5The receptors signaling function is mediated by the beta and gamma chains, which are expressed on T cells (and natural killer cells) constitutively, can be up-regulated by activation and dimerize to bind IL-2 with low affinity.5The alpha chain of the IL-2 receptor (CD25) has no signaling capacity but confers on the receptor the ability to bind IL-2 with high-affinity.5T cell activation induces IL-2 production and upregulates the high-affinity IL-2 receptor subunit CD25, increasing T-cell responsiveness to IL-2.5,9Binding of IL-2 to its high-affinity receptor causes T cells to proliferate about 1,000-fold in the secondary lymphoid organs, producing a large population of lymphoblasts, also termed effector cells.10IL-2 binding to its receptor stimulates increased cytokine synthesis and potentiates Fas-mediated apoptosis. It causes proliferation and activation of NK cells and B-cell proliferation and antibody synthesis. Also, it stimulates the activation of cytotoxic lymphocytes and macrophages.11IL-2R signaling influences two discrete aspects of immune responses by CD8(+) T cells, terminal differentiation of effector cells in primary responses and aspects of memory recall responses.9IL-2 is produced mainly by CD4b helper T cells5and a subset of CD8 cells.12T cells that express high levels of CD25 are essential for maintaining self-tolerance. A class of T cells, known as regulatory T cells (Tregs), are defined by the co-expression of CD25 and the transcription factor forkhead box P3 (FOXP3).5,9Studies indicate that IL-2 not only stimulates immune responses and generates effector cells but also is required for Treg-mediated suppression of immune responses.5A major and essential function of IL-2 is to maintain self tolerance and prevent autoimmunity, and depletion or decreased production of this cytokine is associated with systemic autoimmunity.5Although exposure of a memory CD8 cells to their cognate antigen generally induces reactivation and cytotoxicity, sustained antigen exposure during chronic infection and cancer can cause exhaustion.13Exhausted CD8 T-cells lose effector function, fail to self-renew and have defective memory responses. They are characterized by high expression of inhibitory receptors, expression of specific transcriptional regulators and metabolic dysfunction. While T cell exhaustion is undesirable in the setting of infection and malignancy, it can protect from autoimmunity. Both soluble and cellular mediators can regulate exhaustion in CD81 T-cells. IL-10 can induce exhaustion, whereas IL-2 can promote or repress exhaustion depending on the timing and duration of exposure.12A meta-analysis found that elevated IL-2 was strongly associated with acute respiratory distress syndrome mortality.14

Autoimmune & Inflammation

Cytokines are low-molecular-weight intercellular signaling molecules that are producedde novoin response to an immune stimulus.1-3They regulate immune cell homeostasis by mediating innate and acquired immunity and inflammation in human health and disease. They generally (although not always) act over short distances and short time spans and at very low concentrations. They act by binding to specific membrane receptors, which then signal the cell via second messengers, often tyrosine kinases, to alter its behavior. Responses to cytokines include increasing or decreasing expression of membrane proteins (including cytokine receptors), proliferation and secretion of effector molecules. It is common for different cell types to secrete the same cytokine or for a single cytokine to act on several different cell types (pleiotropy). Cytokines are redundant in their activity, meaning similar functions can be stimulated by different cytokines. Cytokines are often produced in a cascade, as one cytokine stimulates its target cells to make additional cytokines. Cytokines can also act synergistically (two or more cytokines acting together) or antagonistically (cytokines causing opposing activities).Interleukin-8 (IL-8) is a potent neutrophil-specific chemotactic factor that is an important mediator of the immune reaction in the innate immune system response. In 2002, IL-8 was assigned the name CXCL8 by the Chemokine Nomenclature Subcommittee of the International Union of Immunological Societies.4Its primary receptors were similarly renamed; (IL8 receptor, alpha to CXCR1 and IL8 receptor, beta to CXCR2). IL-8 is expressed in various cell types including neutrophils, fibroblasts, epithelial cells, hepatocytes, alveolar macrophages, airway smooth muscle cells and endothelial cells.5-7Endothelial cells store IL-8 in their storage vesicles, the Weibel-Palade bodies.8,9Increased IL-8 concentrations have been found in inflammatory sites in patients with diseases such as psoriasis, rheumatoid arthritis, respiratory syncytial virus infection, asthma and chronic obstructive pulmonary diseases.10IL-8 mediates its biological effects through the binding to CXC chemokine receptors, CXCR1 and CXCR2, which activates a phosphorylation cascade to trigger chemotaxis and neutrophil activation as part of the inflammatory response.11,12It induces chemotaxis in target cells, primarily neutrophils, causing them to migrate toward the site of infection.13While neutrophil granulocytes are the primary target cells of IL-8, there are a relatively wide range of cells (endothelial cells, macrophages, mast cells and keratinocytes) that respond to this chemokine. IL-8 also stimulates phagocytosis once neutrophils arrived at the site of infection. IL-8 is also known to be a potent promoter of angiogenesis.14Another key function of the cell signaling stimulated by CXCL8 is the initiation of the oxidative burst. This process allows the buildup of proteolytic enzymes and reactive oxygen species (ROS) that are necessary to break down the epithelial basement membrane. The release of ROS and damaging enzymes is regulated to minimize host damage while carrying out it effector functions.13Dysregulated signaling by IL-8 has been implicated as a possible cause of Acute Respiratory Distress Syndrome (ARDS).15-17Patients with pancreatitis who developed ARDS have demonstrated significantly higher serum concentrations of IL-8 expression (indicative of neutrophil activation) compared to patients without ARDS.18Elevated levels of IL-8 have also been reported in patients with transfusion-related acute lung injury (TRALI).19The recent world-wide pandemic of Coronavirus disease 2019 (COVID-19) caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has resulted in a dramatic increase in patients with acute respiratory failure and ARDS, both of which are associated with increased mortality, healthcare cost and post-recovery morbidity.12Neutrophil activation caused by IL-8 has been implicated in the pathogenesis and progression of this disease. In patients with severe COVID-19, IL-8 is one of the main chemokines responsible for recruitment, activation and accumulation of neutrophils. Increased IL-8 levels has been associated with the development of acute kidney injury, a complication of COVID-19, and respiratory failure as shown by a reduction in PaO2/FiO2.20IL-8 has demonstrated to be significantly higher in nonsurvivors compared to survivors of COVID-19, and the dynamic change of the serum IL-8 levels has been correlated with the severity of the disease.21-24IL-8 serum levels have also been shown to correlate better than IL-6 levels with overall clinical disease scores.22,25Elevated serum levels of IL-8 have been associated with longer duration of illness in patients with severe or critical COVID-19.26IL-8 has been associated with the recruitment and activation of polymorphonuclear-myeloid derived suppressor cells (PMN-MDSC) that inhibit the response by T-cells to SARS-CoV-2.27Additionally, the frequency of PMN-MDSCs in critical COVID-19 patients is higher in non-survivors compared with survivors, and the frequency of PMN-MDSCs is positively correlated with plasma levels of IL-8 in hospitalized COVID patients.27IL-8 has been shown to have multiple pro-tumorigenic roles within the tumor microenvironment, including stimulating proliferation or transformation of tumor cells into a migratory or mesenchymal phenotype.28-30Further, IL-8 can increase tumor angiogenesis or recruit larger numbers of immunosuppressive cells to the tumor.28In several malignancies, patients with higher levels of IL-8 at baseline experience worse clinical outcomes.28,31-35Additionally, studies have shown that the chemokine directly contributes to the development of resistance to both chemotherapy and molecularly targeted agents.28More recently, clinical studies evaluating levels of IL-8 in patients receiving immune checkpoint inhibition (ICI) therapy deduced that myeloid tumor infiltration driven by IL-8 contributes to resistance to ICI agents and that peripheral IL-8 can predict outcomes to ICI therapy.28

Autoimmune & Inflammation, Infectious Diseases

IgD (molecular weight 185 kD) is one of the 5 classes of human immunoglobulins. IgD accounts for less than 1% of the total plasma immunoglobulins. Very high serum IgD concentrations can be found in multiple myeloma patients. Raised levels are also found in hyperimmunoglobulinemia IgD syndrome (HIDS).

Autoimmune & Inflammation

Sensorineural hearing loss, commonly referred to as nerve deafness, may be caused by genetic or acquired factors, such as infections, or it can be immunologically mediated. In the majority of SNHL cases, no cause is apparent and such cases are referred to as idiopathic SNHL. Serum antibody tests to anti-68-kD inner ear antigen can aid in identifying these cases. Using the Western blot technique in patients with progressive SNHL found 35% to be positive for a specific anticochlear antibody in their serum. Recent studies have shown that 32% of patients with idiopathic bilateral SNHL are positive by Western blot. Anti-68-kD (hsp-70) antibodies also occur in approximately 60% of patients with bilateral and 35% of patients with unilateral Ménière's syndrome, an inner ear syndrome that affects balance and hearing.

Autoimmune & Inflammation, General Health & Wellness

The indirect immunofluorescent test has three elements to consider in the result:1. Positive or negative fluorescence. A negative test is strong evidence against a diagnosis of SLE but not conclusive.2. The titer (dilution) to which fluorescence remains positive (provides a reflection of the concentration or avidity of the antibody). Many individuals, particularly the elderly, may have low titer ANA without significant disease substantiated after work-up.3. The pattern of nuclear fluorescence (reflecting specificity for various diseases).Cytoplasmic (non-nuclear) staining patterns may also be noted with the IFA methodology.Multiplex ANA detects up to 11 specific antibodies of the 100+ antibodies that may be found in the ANA IFA.

Digestive Health, Autoimmune & Inflammation

Inflammatory bowel disease is a chronic disorder of the lower gastrointestinal tract that may occur in three forms: Crohn's disease (CD), ulcerative colitis (UC), and indeterminate colitis (IC). Its prevalence in the adult population approaches 0.3%.1The differential diagnosis of the different forms of IBD is often difficult, time-consuming, and invasive.2The gold standard for diagnosis is endoscopy with biopsies for histologic examination.3In recent years, however, a number of serological markers have been introduced. The most commonly employed serological markers of IBD are anti-Saccharomyces cerevisiaeantibody (ASCA) and atypical perinuclear antineutrophil cytoplasmic antibody (pANCA). ASCA positivity is found predominantly in patients with CD, while pANCA positivity is found predominantly in patients with UC.2A combination of ASCA and pANCA has a specificity of as high as 99% for differentiation of CD from UC.3Nevertheless, there are a substantial number of patients with IBD who are negative for both. The addition of novel serological markers improves the sensitivity of the conventional ASCA/pANCA combination.3About two-thirds of patients with CD develop either a stricturing or penetrating disease course within 10 years after diagnosis. As many as 80% of all CD patients undergo surgery at least once during the course of their disease. Consequently, the identification of individuals susceptible to the development of more complicated disease behavior would allow for earlier and more aggressive treatment.4This profile offers three novel markers: antichitobioside IgA (ACCA), antilaminaribioside IgG (ALCA), antimannobioside IgG (AMCA), together with anti-Saccharomyces cerevisiaeIgG (gASCA) and pANCA. These markers provide additional diagnostic and prognostic information depending on the combination of results.3-6The antibodies included in the panel are ASCA (anti-Saccharomyces cerevisiaeantibodies), ALCA (antilaminaribioside carbohydrate antibodies), ACCA (antichitobioside carbohydrate antibodies), and AMCA (antimannobioside carbohydrate antibodies).3,5,6Numerous studies of CD have demonstrated an association between ileal disease and the presence of ACCA,3ALCA,3,6AMCA,6and ASCA.3,5-10Among these antibodies, the association with localization to the small intestine increased with the number of positive antibodies and with the concentration of individual antibodies.3,5,6,9,11A more aggressive or complicated disease course in CD (as indicated by stricturing or perforation of the intestine or need for surgery), has also been associated with the presence of ACCA,3,5ALCA,3,5,6AMCA,3,5and ASCA.3,5,6,8-10Among these antibodies, the association with complicated disease behavior or surgery increased with the number and concentration of antibodies.3,5,9,11

Autoimmune & Inflammation

Offered as part of multiple lab tests

Autoimmune & Inflammation

Mannose-binding lectin (MBL) is a multimeric, carbohydrate-binding protein produced in the liver and secreted into the blood that plays an important role in the innate immune response against invading microörganisms.1-6MBL is a member of a family of the "collections" proteins, so named because they have a collagen-like region and a lectin region. Functional MBL is an oligomer complex of three identical monomer chains connected together through a triple helix of the collagen-like regions. The three C-terminal lectin carbohydrate recognition domains of the individual component proteins stick out from the triple helix in a manner that, by electron microscopy, resembles three flowers protruding from a single stalk. Many pathogens, including viruses, bacteria, fungi, protozoa, have surface sugars that are absent from mammalian cell surfaces. The lectin domains of the MBL complex recognize the spatial arrangement of carbohydrate sugar residues on pathogen surfaces and bind to them. Specific enzymes (MBL-associated serine proteases or MASPs) are activated when MBL binds to microbial carbohydrate surfaces and in turn activate complement via the MBL or lectin pathway. MBL binding to pathogens surfaces activates the complement system, causing inflammation, increased vascular permeability, and the recruitment and activation of phagocytes. MBL binding also facilities recognition and ingestion of the foreign entity by phagocytes in a process referred to as opsonization.Only the normally oligomerized forms of MBL are capable of binding efficiently to the microbial carbohydrates and associating with the MASPs, thus activating complement via the lectin pathway. Diminished MBL levels can occur due to allelic variants in the promoter and/or structural regions of the MBL gene. Certain promoter alleles are associated with lower serum concentrations of MBL, while the structural variants impair both normal oligomerization of MBL and total chain synthesis.7Subjects who are homozygous for a structural defect show very low levels of oligomerized MBL (<50 ng/mL), while heterozygotes show low-intermediate levels (50−500 ng/mL). In 100 healthy Danish blood donors, serum MBL concentrations determined by an oligomer-selective immunoassay showed low values (<50 ng/mL) in 12 individuals.8Sallenbach and coworkers measured the MBL serum concentration in 631 apparently healthy subjects.9The median MBL serum concentration was 1340 ng/mL (range, <5-12,200). Results were below the detection limit in 40 (11.4%) of 350 adults, in 1 of 141 preterm, and in 1 of 20 term neonates.9Eisen and coworkers suggested that a cutoff of 500 ng/mL would be an appropriate threshold for identifying patients with MBL-deficient genotypes.10Most individuals with diminished levels of normally oligomerized MBL are healthy with no clinical evidence of immune deficiency.11While the consequences of MBL deficiency can be quite subtle, several studies have shown that MBL deficiency increases the overall susceptibility of an individual to infectious disease and predisposes to greater severity when infections occur. Decreased MBL levels may be associated with increased susceptibility to infections when the adaptive immune system is immature (in early childhood)12or has been suppressed after organ transplantation13-15or during cancer chemotherapy.16,17In adults, MBL may play a role in determining host susceptibility to infection, pathogenesis, and progression of disease, and may contribute to the variability of host response to infection.10,18-20Studies also suggest that individuals with relatively low MBL may suffer from more severe courses of autoimmune diseases such as systemic lupus erythematosus21,22or rheumatoid arthritis,23and from poorer prognoses in cystic fibrosis.24Recurrent spontaneous abortions are reported to be correlated with low serum MBL levels.25,26It has also been shown that low serum MBL levels have a negative impact on pregnancy outcome in women with a history of unexplained recurrent spontaneous abortion.27

Autoimmune & Inflammation

Autoantibodies to RNA Polymerase III antigen are found in 11% to 23% of patients with systemic sclerosis. Patients who are positive for RNA Polymerase III antibodies do not have any of the other antibodies typically found in systemic sclerosis patients such as anti-centromere, anti-Scl-70, or anti-Pm/Scl antibodies. Thus, they are a separate serologic group. Numerous studies have shown that these patients have an increased risk of the diffuse cutaneous form of scleroderma, with high likelihood of skin involvement and hypertensive renal disease.Antibodies to several different types of RNA Polymerases are found in patients with systemic sclerosis. The immunodominant epitope or RNA Pol III was identified and cloned. The recombinant immunodominant epitope of RNA Pol III can be used in ELISA with high specificity to detect anti-RNA Pol III antibodies in patients with the diffuse cutaneous form of systemic sclerosis, with a high incidence of skin involvement.

Autoimmune & Inflammation

Offered as part of multiple lab tests

Autoimmune & Inflammation, General Health & Wellness

Offered as part of multiple lab tests

Autoimmune & Inflammation

Chlamydia trachomatisis associated with infections of the mucous membranes of the urogenital system, the upper respiratory tract, and the eye.The usefulness of serological tests depends on the site of infection, duration of disease, infecting serovars and previous exposure to chlamydial antigens. BecauseC. trachomatisis ubiquitous, there is a high prevalence of antibodies in sexually active populations. Individuals may be reinfected and IgM antibodies may not appear. IgG antibodies may persist even after treatment, making assessment of a single IgG titer difficult. Consequently, serological diagnosis is seldom used to diagnose genital tract infections. Instead, Nucleic Acid Amplification Testing (NAAT) or culture should be considered to detect chlamydia trachomatis. Culture can also be used to diagnose infant respiratory infection or conjunctivitis.

Autoimmune & Inflammation, Heart Health & Cardiovascular

Lupus anticoagulants are nonspecific antibodies that extend the clotting time of phospholipid-dependent clotting assays such as the aPTT.6,7Unlike specific factor antibodies, LA are usually associated with venous thrombosis, pulmonary embolism, arterial thrombosis, and recurrent fetal loss.8LA do not specifically inhibit individual coagulation factors; rather they neutralize anionic phospholipid-protein complexes that are involved in the coagulation process. Prolongation of clot-based assays is highly dependent on the sensitivity of the reagent employed. Reagents with reduced amounts of phospholipid, such as the aPTT-LA and dilute Russell viper venom time (dRVVT), have enhanced sensitivity for LA.6Due to the heterogeneity of LA antibodies, no single assay will identify all cases.8The International Society on Thrombosis and Haemostasis (ISTH) has established criteria for the diagnosis of lupus anticoagulants.6-8Testing for lupus anticoagulant (LA) and the antiphospholipid syndrome that is associated with these antibodies is described in more detail in the online Coagulation Appendices: Lupus Anticoagulants and Antiphospholipid Syndrome.

Heart Health & Cardiovascular, Autoimmune & Inflammation

Useful in predicting risk of cardiovascular disease.

Autoimmune & Inflammation

Offered as part of multiple lab tests

Autoimmune & Inflammation

Cytokines are low-molecular-weight intercellular signaling molecules that are producedde novoin response to an immune stimulus.1-3They regulate immune cell homeostasis by mediating innate and acquired immunity and inflammation in human health and disease. They generally (although not always) act over short distances and short time spans and at very low concentrations. They act by binding to specific membrane receptors, which then signal the cell via second messengers, often tyrosine kinases, to alter its behavior. Responses to cytokines include increasing or decreasing expression of membrane proteins (including cytokine receptors), proliferation and secretion of effector molecules. It is common for different cell types to secrete the same cytokine or for a single cytokine to act on several different cell types (pleiotropy). Cytokines are redundant in their activity, meaning similar functions can be stimulated by different cytokines. Cytokines are often produced in a cascade, as one cytokine stimulates its target cells to make additional cytokines. Cytokines can also act synergistically (two or more cytokines acting together) or antagonistically (cytokines causing opposing activities).T Helper cells (THcells), also known as CD4+ cells or CD4-positive cells, play an important role in the adaptive immune system. They are essential in B cell antibody class switching,4,5,6breaking cross-tolerance in dendritic cells, activation and growth of cytotoxic T cells, and in maximizing bactericidal activity of phagocytes such as macrophages and neutrophils. IL-4 acts on both B and T cells. It is a B-cell growth factor and causes IgE and IgG1 isotype selection.7It causes TH2 differentiation and proliferation, and it inhibits IFN gamma-mediated activation on macrophages. It promotes mast cell proliferationin vivo.8Naive THcells (T0 cells) differentiate into two major THhelper subtypes, referred to as TH1 and TH2 cells. TH2 cells produce interleukin-4 (IL-4) along with IL-5 and IL-13.2,9Peripheral TH0 cells, upon recognition of antigenic peptides by the T cell receptor (TCR), migrate into lymphoid tissues and functionally differentiate into different THcell subsets.10IL-4 promotes TH2 immune response by inducing the differentiation of TH0 cells to TH2 cells in a positive feedback loop.11IL-4 induces TH2 cell differentiation in an autocrine manner at inflammatory sites.12TH2 cells gain full effector capacity in tissues by interacting with various local cells, including innate lymphoid cells and neurons, which produce TH2-promoting factors in response to allergens, helminths and other stimuli.2,10In addition to TH2 cells, mast cells, eosinophils and basophils produce IL-4.13-15Eosinophils produce IL-4 in the very early stage of the immune response in lymph nodes and tissues and can induce TH2 differentiation by antigen presentation to CD4+ T cells.10Fibroblasts play an important role in normal tissue repair and the induction of fibrosis by directly depositing extra cellular matrix in response to various growth factors and cytokines, including TH2 cytokines.10Macrophages that are activated by IL-4 and IL-13 have been reported to induce fibrosis by various mechanisms.IL-4 is the most common cytokine produced by TH2 lymphocytes and the key cytokine that regulates TH2 cell polarization.12,16In addition, IL-4/IL-4R signaling promotes B cell proliferation and stimulates immunoglobulin class-switching to IgE antibody, the major antibody in allergic reactions.12,16Production of these cytokines by TH2 lymphocytes and other cells accounts for the activation of the mast cells, basophiles, eosinophiles and smooth muscle cell contraction as well as stimulation of B cell differentiation into IgE-producing plasma cells, thus promoting several allergic reactions including allergic rhinitis, anaphylaxis, atopic dermatitis and asthma.12,16,17TH2 cells are often observed in tissues in allergic patients and are known to play critical roles in the pathogenesis of allergic diseases.9,12,18-22Allergic diseases are characterized by aberrant activation of TH2 cells in response to innocuous environmental proteins (allergens)23and subsequent production of Type 2 cytokines at sites of allergic inflammation.24,25These reactions involve inflammatory mediators released in the early-phase reaction by mast cells and basophils, and allergen-specific TH2 lymphocytes.26TH2 cells act synergistically with type 2 innate-like lymphoid cells activated during the acute phase. They recruit effector cells such as eosinophils, basophils, as well as other lymphocytes, to the site of allergen exposure.27-29IL-4, IL-5, and IL-13 drive TH2 cells towards a specialized TH2A phenotype associated with persistent allergy and high cytokine expression.30,31Asthma is a heterogeneous disease that can be classified into phenotypes and endotypes based upon clinical or biological characteristics.13,32-34IL-4, along with IL-13, plays a key role in TH2 asthma.32Over expression of IL-4 in asthmatics is associated with exacerbations, compromised lung function, airway remodeling and airway epithelium injury.35Approximately 50% of mild-to-moderate asthma and a large portion of severe asthma is associated with TH2-dependent inflammation.33IL-4 mediates pro-inflammatory functions in asthma, including induction of the expression of vascular cell adhesion molecule-1 (VCAM-1), promotion of eosinophil transmigration across endothelium and mucus secretion.36,37TH2 inflammation is characterized by elevations in absolute peripheral or sputum eosinophil counts and levels of IgE (total and allergen-specific) and fractional exhaled nitric oxide, which serve as biomarkers for the presence of this type of inflammation.13Compared with healthy controls, children and adults with asthma have higher serum levels of IL-4,38,39and higher IL-4 levels may differentiate individuals with atopic asthma from those with nonatopic asthma.38,39Persistence of asthma in children and adults may be predicted by elevated levels of IL-4.19,20IL-4 regulates the protective immune response against helminths and other extracellular parasites.3,7Plasma levels of IL-4 have been reported to be elevated in patients with eosinophilic esophagitis, indicating the role of adaptive TH2 immunity in this disease.40A meta-analysis found that elevated IL-4 was strongly associated with acute respiratory distress syndrome mortality.41There have been extensive clinical trials targeting IL-4 for the treatment of asthma.24Modulation of IL-4 signaling42represents an important therapeutic approach to target the drivers of allergy and asthma.18,42-45Dupilumab targets the shared receptor for IL-4 and IL-13 and is approved for treatment of atopic dermatitis and asthma.2Dupilumab has been shown to provide efficacy in the treatment of moderate-to-severe atopic dermatitis, allergic asthma, chronic rhinosinusitis and eosinophilic esophagitis, all known to be driven largely by type 2 inflammation.18,43-45IL-4 and IL-13 produced by TH2 cells activate macrophages and epithelial cells and enhance the production of extracellular matrix, an element crucial for tissue repair.10However, when the tissue repair process becomes chronic, excessive or uncontrolled, it may induce the development of pathological fibrosis in various organ systems.10It was recently shown that TH2 cells include pathogenic TH2 (Tpath2) cells that highly express the receptor for IL-33 (a cytokine that is released during tissue injury) and produce large amounts of IL-5.9,10

Autoimmune & Inflammation, Allergy Testing

Cytokines have emerged as molecules of importance in the regulation of many immunologic processes in the cell. The ability to accurately measure QN and QL differences in cytokine production is becoming increasingly important to the understanding of normal and pathological processes.

Autoimmune & Inflammation

The antiphospholipid syndrome (APS) is a unique form of acquired autoimmune thrombophilia characterized by recurrent arterial and/or venous thrombosis, pregnancy-related complications (including miscarriages, fetal deaths, premature births, and preeclampsia), and the persistent presence of antiphospholipid antibodies (aPL).2The original APS classification criteria required positivity for any one of 1) anticardiolipin (aCL) IgG or IgM antibodies or 2) lupus anticoagulant (LA) as diagnostic laboratory criteria.3In 2006, the sensitivity of the classification criteria was improved by the including positivity for 3) β2-glycoprotein 1 (β2GPI) IgG or IgM antibodies as additional laboratory criteria for APS and the specificity of diagnosis was improved by extending the requirement of persistent presence of aPL to 12 weeks.4At least one clinical (vascular thrombosis or pregnancy morbidity) and one lab-based (positive test result for LA, aCL IgG/IgM or β2GPI IgG/IgM) criterion have to be met for a patient to be classified as having APS.The antibodies associated with APS are known to react with phospholipids and/or with their binding proteins, either independently or in phospholipid–protein complexes. Early assays for antibodies to the lipid anticardiolipin were quite non-specific and were eventually replaced with assays employing complexes of cardiolipin with the protein β2GPI.2,5Assays for antibodies to β2GPI have been shown to be more specific for APS albeit with somewhat lower sensitivity. Antibodies to prothrombin (aPT), have also been shown to occur in patients with APS.6-12A large amount of data obtained mainly from retrospective studies provides contrasting evidence concerning the clinical significance of aPT antibodies.13-16It has been shown that aPT associated with LA activity or APS clinical manifestations can be detected only using assays employing purified PT antigen immobilized on irradiated plates or as a complex with the lipid phosphatidylserine (aPS/PT).10,11,14,17,18A systematic review and meta-analysis of 10 studies performed before 2014 found that aPS/PT antibody positivity is a strong risk factor for thrombosis and venous events independent from sites and type of thrombosis.6A more recent meta-analysis, published in 2020,19reviewing 15 studies published since the 2014 analysis20-34further confirmed the association between aPS/PT antibodies and thrombosis. Pooled analysis revealed a significant association between aPS/PT-IgG/IgM21-23,31,32,34and thrombotic events with mean Odds Ratio (mOR = 6.8) relative to controls. Pooled analysis further found an association between thrombotic events and aPS/PT-IgG6,20,22-29,31-34positivity (mOR = 6.7) and aPS/PT-IgM20-23,25,28-32,34positivity (mOR = 4.35). A subset of studies,21,24,26,27,31-33including 1,388 patients, evaluated the association between aPS/PT antibodies and pregnancy morbidity (PM) as defined by the 2006 criteria for the definition of APS.4Pooled analysis of the results from these studies found a statistically significant association between any PM and aPS/PT IgG/IgM positivity (mOR = 10.6) and, specifically, aPS/PT IgG positivity (mOR = 6.7).19While the tests currently included in the classification criteria for APS are able to detect the great majority of the cases, some patients present clinical manifestations highly suggestive of APS while being persistently negative for the aPL tests included in the guidelines.1,35-39These patients have been termed to have seronegative APS (SNAPS).36,37,40Testing for aPS/PT antibodies has been proposed as an additional tool to be considered when investigating a patient suspected of having APS, particularly in the absence of guideline aPL positivity9,26,28,32,36,37,40-48or as a part of risk assessment strategies.49A number of studies have found that approximately 50 percent of patients with SNAPS were positive for IgG and/or IgM aPS/PT.33,35,37,39,50,51The addition of aPS/PT to current criteria aPL assays has been reported to contribute to the identification of patients with a history of thrombosis and/or pregnancy-related morbidity that would go undiagnosed using current criteria aPL assays.21,23,32,36,37,42,45,52-56In a number of studies, aPS/PT positivity was reported to be an independent risk factor for LA activity and to occur in LA-negative SLE or APS patients with thrombosis and pregnancy loss.23,54,56Other investigators comparing different aPL combinations in patients with systemic lupus erythematosus observed that aPS/PT antibodies were significantly associated with both LA and pregnancy-related morbidity, while the combination of LA, anti-β2GPI and aPS/PT had superior diagnostic accuracy for thrombosis and pregnancy loss in APS.57,58These studies suggest that aPS/PT and LA are, at least in part, independent risk factors for clinical manifestations of APS. A recent study demonstrated that determination of aPS/PT antibodies in concert with β2GPI antibodies in patients positive for LA might be useful for identifying patients at different risk of thromboembolic events.59In addition, patients with triple positivity for LA, β2GPI and aPS/PT have been shown to be at a higher risk of developing thromboembolic events, risk even higher than that seen for the “classical” aCL, β2GPI and LA triple positivity.52,58aPS/PT have been shown to be associated with recurrent early or late abortions and with premature delivery irrespective of other aPL.51aPS/PT positivity also has been found to be predicative of non-criteria clinical symptoms4including thrombocytopenia or hemolytic anemia.34In addition to diagnosis, use of biomarkers to help predict risk of thrombosis has been addressed by the development of the anti-PhosphoLipid-Score (aPL-S) and the Global APS Score (GAPSS), Both these scoring systems include levels of aPS/PT antibodies (and not PS or PT) as components of the scoring system.19,48,49,60,61

Autoimmune & Inflammation

Celiac disease is a multigenic immune-mediated enteropathy triggered by dietary proteins, commonly known as glutens, present in wheat, barley, and rye. Varied clinical manifestations begin either in childhood or adult life. Its prevalence in the united states ranges from 0.5 to 1%. Celiac disease is strongly associated with the HLA genetic region. Approximately 90% of celiac patients express the HLA-DQ2 molecule. Most of the DQ2 negative patients express the HLA-DQ8 molecule. Gluten peptides presented by these HLA molecules induce an abnormal mucosal immune response and tissue damage.  The HLA-DQ molecules are heterodimers of an alpha and a beta chain. The beta chain of HLA-DQ2 is coded by HLA-DQB1*02 and of DQ8 by HLA-DQB1*0302. HLA-DQB1 genotyping allows clinicians to evaluate the genetic predisposition for celiac disease in a patient.

Autoimmune & Inflammation

This assay may be useful in supporting or ruling out a diagnosis of rheumatoid arthritis.

Infectious Diseases, Autoimmune & Inflammation

PCT is the prohormone of the hormone calcitonin, but PCT and calcitonin are distinct proteins. Calcitonin is exclusively produced by C-cells of the thyroid gland in response to hormonal stimuli, whereas PCT can be produced by several cell types and many organs in response to proinflammatory stimuli, in particular by bacterial products.1In healthy people, plasma PCT concentrations are found to be below 0.1 μg/L.2Depending on the clinical background, a PCT concentration above 0.1 μg/L can indicate clinically relevant bacterial infection, requiring antibiotic treatment.3PCT levels rise rapidly (within 6 to 12 hours) after a bacterial infectious insult with systemic consequences. The magnitude of the increase in PCT concentration correlates with the severity of the bacterial infection.4At a PCT concentration >0.5 μg/L, a patient should be considered at risk of developing severe sepsis or septic shock.5,6On the other hand, the relief of the septic infection is accompanied by a decrease in the PCT concentration which returns to normal with a half-life of 24 hours,7,8(ie, the continuous decline of PCT is indicative of effective source control measures and has been implicated in the safe deëscalation of antibiotic therapy).9,10Data support the following interpretative risk assessment criteria11,12,13:PCT > 2 ng/mL: A PCT level above 2.0 ng/mL on the first day of ICU admission is associated with a high risk for progression to severe sepsis and/or septic shock.PCT < 0.5 ng/mL: A PCT level below 0.5 ng/mL on the first day of ICU admission is associated with a low risk for progression to severe sepsis and/or septic shock.Note: Concentrations < 0.5 ng/mL do not exclude an infection, on account of localized infections (without systemic signs) which can be associated with such low concentrations, or a systemic infection in its initial stages (< 6 hours).Furthermore, increased procalcitonin can occur without infection. PCT concentrations between 0.5 and 2.0 ng/mL should be interpreted taking into account the patient's history. It is recommended to retest PCT within 6-24 hours if any concentrations < 2 ng/mL are obtained.The change of PCT concentration over time (Delta PCT) provides prognostic information about the risk of mortality14within 28 days for patients diagnosed with severe sepsis or septic shock coming from the emergency department, ICU, other medical wards, or directly from outside the hospital. Data support the use of PCT determinations from the day severe sepsis or septic shock is first diagnosed (Day 0) or the day thereafter (Day 1) and the fourth day after diagnosis (Day 4) for the classification of patients into higher and lower risk for mortality within 28 days. The Delta PCT is calculated in the manufacturer's package insert for the Elecsys BRAHMS PCT11as:The change in PCT (Day 0 value minus Day 4 value) divided by the Day 0 value, all multiplied by 100%.This calculated result is interpreted as follows:Delta PCT ≤ 80 %: A decrease of PCT levels below or equal to 80 % defines a positive ΔPCT test result representing a higher risk for 28-day all-cause mortality of patients diagnosed with severe sepsis or septic shock.Delta PCT > 80 %: A decrease of PCT levels of more than 80 % defines a negative ΔPCT result representing a lower risk for 28-day, all-cause mortality of patients diagnosed with severe sepsis or septic shock.Notes:• If Day 0 result is not available, Day 1 result may be used.• If more than one PCT value is available on Day 0 (or Day 1), enter the highest value.• If more than one PCT value is available on Day 4, enter the most recent value.

Digestive Health, Autoimmune & Inflammation

Celiac disease is a gluten enteropathy occurring in both children and adults. The disease is probably underdiagnosed in that it may affect as much as 1% of the population in the United States. The condition is characterized by a sensitivity to gluten (found in wheat, barley, and rye) that causes inflammation and atrophy of the villi of the small intestine, malabsorption, etc. This sensitivity to gluten may also be seen in dermatitis herpetiformis. Strict avoidance of gluten in the diet will control disease activity, and antibodies to serum markers will disappear with time.

Digestive Health, Autoimmune & Inflammation

Disorders of the lower gastrointestinal tract in adults and children are among the most common conditions and may pose a difficult diagnostic problem. They account for 1 in 20 of all general practitioner consultations and their symptoms are frequently ill-defined.1Those disorders include a wide range of pathologic conditions, including irritable bowel syndrome (IBS), inflammatory bowel disease (IBD) that includes Crohn's disease (CD), ulcerative colitis (UC), and indeterminate colitis; microscopic colitis, infectious colitis, small intestinal bacterial overgrowth, celiac disease, and colon neoplasia (including colon cancer).2The most prevalent condition is IBS. Its prevalence in Europe and North America is estimated to be 10% to 15%.3Prevalence of celiac disease increased at least four times during the last 50 years and approaches 0.9%.4The incidence rate of Crohn’s disease increased from 0.1 (three decades ago) to 4.6 (in 2003) per 100,000 children and the incidence of UC from 0.5 to 3.2 per 100,000 children.5The prevalence of IBD in the adult population is approaching 0.3%.6Recently another condition termed “gluten sensitivity” emerged as an important and often underdiagnosed and undertreated disease.7-11It is reported that as many as 12% of the healthy population may have serological evidence of gluten sensitivity.9Difficulties in differential diagnosis of those conditions often prompt clinicians to use an exclusion approach by performing tests to rule out the alternative etiologies.2Interestingly, one study shows that most of the celiac disease serological test requests are now from general practitioners rather than gastroenterologists.12Another study reports that 72% of general practitioners endorsed IBS as a diagnosis of exclusion.2Endoscopy with biopsies for histological examination remains the gold standard for the diagnosis of many of these conditions.13In recent years, however, introduction of a number of new and improved serological tests may allow for reduction in the number of intestinal biopsies.14The cascade includes three testing steps:Step 1: Celiac Disease Screen:The cascade begins with a celiac screen that includes testing for tTG IgA and DGP IgG.10When any or both of the results are positive, the testing stops and the interpretive comment on the report would read: “Suggestive of celiac disease or other gluten-sensitive enteropathies. Subsequent testing forEndomysial Antibody, IgA [164996]and/or genetic testing forCeliac Disease HLA DQ Association [167082]may be indicated for further patient evaluation.” When the result is negative, the testing reflexes to the second step.Step 2: Inflammatory Bowel Disease Screen:Inflammatory bowel disease screen includes testing for IgG antibodies to anti-Saccharomyces cerevisiae(ASCA) and atypical perinuclear antineutrophil cytoplasmic antibodies (pANCA). This profile of tests aids in the serological identification of patients with IBD and in differentiation among its three clinical forms: CD, UC, and indeterminate colitis. When the marker for CD (ASCA IgG) is positive, the clinical sensitivity for CD is reported to be as high as 74.4% and specificity for IBD as high as 94.4%.15When atypical pANCA (a marker of UC) is positive, the clinical sensitivity for UC is reported to be as high as 70% and specificity as high as 80%.16It must be emphasized that neither of the markers negatively rules out IBD. Similarly, the presence of these antibodies does not strictly confirm the diagnosis of IBD.17Testing for Step 2 is described below and (depending on the combination of results) the interpretive comment on the report would be one of the following: When ASCA IgG is positive and atypical pANCA is negative, testing stops and the comment would read: “Suggestive of Crohn's disease. Subsequent testing with theCrohn's Disease Prognostic Profile [162020]that includes antiglycan antibodies AMCA, ALCA, ACCA, and gASCA may aid in the differentiation of clinical forms of CD and prognosis of disease progression.” When ASCA IgG is negative or equivocal and atypical pANCA is positive testing stops and the comment would read: “Suggestive of ulcerative colitis.” When both ASCA IgG and atypical pANCA are positive testing stops and the comment would read: “Suggestive of IBD. Subsequent testing with theCrohn's Disease Prognostic Profile [162020]that includes antiglycan antibodies AMCA, ALCA, ACCA, and gASCA may aid in the differentiation of clinical forms of IBD and prognosis of disease progression.” When all results are negative, then the testing reflexes to the third step.Step 3: Nonceliac Gluten Sensitivity Screen:The nonceliac gluten sensitivity screen includes testing for IgG antibodies to gliadin with reported clinical sensitivity as high as 87% (for untreated clinically defined celiac disease patients) and specificity as high as 91%.18Recent reports show that there is a significant subset of patients who have normal histology for celiac disease, negative for antibodies to DGP and tTG, positive for antigliadin antibodies and clinically indistinguishable from those with celiac disease. Those patients constitute the so-called “nonceliac gluten sensitivity” group, and many of them will benefit from a gluten-free diet. This group of patients is also reported to have increased mortality.7-10,14When the result is positive, the testing stops and the interpretive comment on the report would read: “Suggestive of nonceliac gluten sensitivity. The patient may benefit from a gluten-free diet.” When all results are negative, the testing stops and the interpretive comment on the report would read: “Suggestive of irritable bowel syndrome (IBS). Careful evaluation of the patient's history, physical examination, and application of Rome III diagnostic criteria may help to rule in or rule out the diagnosis of IBS. Subsequent testing forCalprotectin, Fecal [123255]may be recommended. If IBD is strongly suspected, subsequent testing with theCrohn's Disease Prognostic Profile [162020]that includes antiglycan antibodies AMCA, ALCA, ACCA, and gASCA may aid in differential diagnosis.”

Hormone Testing, Autoimmune & Inflammation

Offered as part of multiple lab tests

Autoimmune & Inflammation

Myasthenia Gravis is a neurological disorder characterized by a decrease in acetylcholine receptors. Patients exhibit skeletal muscle weakness and fatigability. Approximately 80% of patients with Myasthenia Gravis, excluding ocular involvement only, have detectable acetylcholine receptor antibody.

Autoimmune & Inflammation

This panel can be helpful in the diagnosis and management of systemic lupus erythematosus (SLE). The panel simultaneously tests for antinuclear antibodies (ANAs) with an immunofluorescence assay (IFA), performed on human epithelial type 2 (HEp-2) cells, as well as 6 specific autoantibodies associated with SLE and 3 biomarkers associated with disease activity. For specimens with positive ANA IFA results, reflex testing for ANA titer and pattern is performed.The ANA testing has high sensitivity (97%) for SLE but limited specificity (34%) [1]. Anti-dsDNA and anti-Sm antibodies are less sensitive but more specific; tests for both antibodies are included in classification criteria for SLE [2]. Anti-chromatin antibodies have relatively high sensitivity and specificity. Although antibodies to SSA and SSB may also be seen in Sjogren Syndrome and anti-RNP is a marker of mixed connective tissue disease, these antibodies are also frequently present in SLE and may be helpful.The results of this test should be interpreted in the context of pertinent clinical and family history and physical examination findings.References1. Petri M, et al.Arthritis Rheum. 2012;64(8):2677-2686.2. Aringer M, et al.Ann Rheum Dis. 2019;78(9):1151-1159.

Autoimmune & Inflammation, Infectious Diseases

Primary immunodeficiencies result from congenital defects of the immune system. Acquired immunodeficiency syndrome (AIDS) results from infection with the HIV-1 retrovirus. The purpose of flow cytometric enumeration is to determine whether select lymphocyte subsets are reduced or absent in order to support the diagnosis of numeric cellular immunodeficiency rather than immunodeficiency due to cellular dysfunction.HIV-1 infection results in a decrease of CD4 T cells, an increase of CD8 T cells, a decrease in the CD4:CD8 ratio, and a progressive destruction of immune function. In HIV-1 seropositive patients, enumeration of CD4 T cells may be used for prognostic purposes and to monitor disease progression and antiretroviral therapy.

Autoimmune & Inflammation, Cancer Screening

Interleukin-2 (IL‑2) stimulates an immune response on target cells via a high affinity receptor (IL-2R) composed of alpha, beta and gamma subunits.5,6The alpha subunit (also referred to as CD25) has no signaling capacity but confers on the receptor the ability to bind IL-2 with high-affinity.6Signals from this receptor activate transcription factors that promote cell survival and proliferation, the two principal actions of IL-2.6Upon antigen stimulation, T cells both produce and respond to IL-2, leading to the preferential expansion of antigen-specific clones. IL-2R is also expressed on regulatory T cells (Tregs), cells that are essential for maintaining self-tolerance, and their depletion results in autoimmunity.6A soluble form of the IL-2R alpha subunit (sIL-2Rα) is released into the serum from the membranes of activated lymphocytes after shedding by proteolytic cleavage.7Release of sIL-2Rα is proportional to the cell surface expression of IL-2R.8sIL-2Rα is detected in the serum of healthy individuals and increases in association with various types of inflammation or neoplasms.5,9-11Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome of excessive immune system activation driven mainly by high levels of interferon gamma.2HLH is induced by aberrantly activated macrophages and cytotoxic T cells.12The primary (genetic) form, caused by mutations affecting lymphocyte cytotoxicity and immune regulation, is most common in children, whereas the secondary (acquired) form is most frequent in adults.12Guidelines for the diagnosis and prognostication of HLH include the measurement sIL-2Rα.13-17Since T-cell activation is central to HLH pathogenesis, elevated sIL-2Rα is almost always observed in untreated HLH.18-20Secondary HLH is commonly triggered by infections or malignancies but may also be induced by autoinflammatory or autoimmune disorders, in which case it is called macrophage activation syndrome.12,21Patients may present with a phenotype indistinguishable from sepsis or multiple organ dysfunction syndrome.12It has been suggested that sIL-2Rα can be a useful marker for the prognosis of patients with HLH that might help to stratify therapeutic interventions.22Since T-cell activation is a hallmark of granuloma formation, diseases with extensive granulomatous lesions often present with elevated sIL-2Rα levels. sIL-2Rα has been reported to be an effective marker for measuring disease in patients with tuberculosis, sarcoidosis eosinophilic granulomatosis with polyangiitis and common variable immunodeficiency.4,23-28Elevated levels have been reported in T-cell mediated diseases including multiple sclerosis, type 1 diabetes mellitus, and rheumatoid arthritis.29-33Increased sIL-2Rα have also been reported in classical autoantibody mediated diseases including myasthenia gravis and pemphigus.34,35Serum sIL-2Rα levels have been found to be elevated in most types of hematolymphoid neoplasms, including Hodgkin's lymphomas, non‑Hodgkin lymphomas, acute lymphoblastic leukemia, chronic lymphocytic leukemia, multiple myeloma, and others.1The highest levels of sIL-2Rα have been reported in adult T‑cell lymphoma/leukemia36and hairy cell leukemia.37Elevated levels have been reported in follicular and diffuse large B-cell lymphoma.5,38-43An extremely elevated sIL-2Rα (>10- to 20-fold above normal) in a non-infantile patient suggests undiagnosed lymphoma, especially when ferritin is not similarly elevated.44,45An association between increased levels of sIL-2Rα and poor outcome has also been reported in several non-lymphoid cancers.1,33,46

Mental Health & Neurological, Autoimmune & Inflammation

Offered as part of multiple lab tests

Autoimmune & Inflammation, Drug & Alcohol Testing

In the absence of antiadalimumab antibodies, the adalimumab drug level typically reflects the total adalimumab concentration in serum. In the presence of antiadalimumab antibodies, the adalimumab level typically reflects the antibody-unbound fraction of adalimumab concentration in serum.This assay provides clinically valid antibody results at drug levels well above treatment targets (>30 μg/mL). Failure of adalimumab therapy may not always be due to the presence of antiadalimumab antibodies. In addition, the absence of antiadalimumab antibodies does not guarantee positive response to treatment.

Autoimmune & Inflammation, Drug & Alcohol Testing

In the absence of antiadalimumab antibodies, the adalimumab drug level typically reflects the total adalimumab concentration in serum. In the presence of antiadalimumab antibodies, the adalimumab level typically reflects the antibody-unbound fraction of adalimumab concentration in serum.This assay provides clinically valid antibody results at drug levels well above treatment targets (>30 μg/mL). Failure of adalimumab therapy may not always be due to the presence of antiadalimumab antibodies. In addition, the absence of antiadalimumab antibodies does not guarantee positive response to treatment.

Autoimmune & Inflammation

Vasoactive intestinal polypeptide (VIP) is a neurohormone produced in the central nervous system as well as in the neurons of the gastrointestinal (GI), respiratory and urogenital tracts.1The main effects of VIP include relaxation of smooth muscle (bronchial and vascular dilation), stimulation of gastrointestinal water and electrolyte secretion and release of pancreatic hormones.2,3VIP secreting tumors (VIPoma) is a rare functional neuroendocrine tumor that typically arises from pancreatic islet cells.4-10The VIPoma syndrome is also known as Verner-Morrison syndrome, watery diarrhea, hypokalemia, and hypochlorhydria or achlorhydria (WDHA) syndrome, and pancreatic cholera syndrome.1VIPomas are functional neuroendocrine tumors that secrete excessive amounts of VIP. VIPoma tumors present as sporadic, solitary pancreatic neoplasias with an estimated incidence of one in ten million individuals per year.11Approximately five percent of VIPomas are associated with multiple endocrine neoplasia type I syndrome.12Excessive VIP secretion produces a clinical syndrome characterized by refractory watery diarrhea, hypokalemia and achlorhydria. These symptoms, coupled with elevated plasma levels of VIP, are diagnostic. The majority of VIPomas are malignant and have already metastasized at the time of diagnosis.

Autoimmune & Inflammation

Offered as part of multiple lab tests

Autoimmune & Inflammation

Myasthenia Gravis is a neurological disorder characterized by a decrease in acetylcholine receptors. Patients exhibit skeletal muscle weakness and fatigability. Approximately 80% of patients with Myasthenia Gravis, excluding ocular involvement only, have detectable acetylcholine receptor antibody. There is a strong correlation between the presence of striated muscle antibody and the presence of thymoma.

Autoimmune & Inflammation

Offered as part of multiple lab tests

Mental Health & Neurological, Autoimmune & Inflammation

Neuromyelitis optica (NMO), also known as Devic's disease, is an immune-mediated neurologic disorder that causes very severe, often bilateral, optic neuritis and longitudinally extensive spinal cord lesions.2,3Historically, NMO was thought to be a form of multiple sclerosis;3however, the nerve damage suffered by patients with NMO has been shown to be distinct from that found in patients with multiple sclerosis.2-4Patients with NMO can present with a variety of symptoms, including visual impairment, muscle weakness, reduced peripheral sensation, and loss of bladder and/or bowel control.5NMO typically follows a relapsing course without marked remission between flare-ups. Neural damage tends to be cumulative, resulting in rapid progression of disability and the development of irreversible deficits.6Recently, antibodies to the most abundant water channel in the central nervous system, aquaporin-4 (AQP4), have been found in patients with NMO.1These antibodies, referred to as AQP4-Ab or NMO-Ab, have been detected in 60% to 90% of patients with NMO and have been shown to correlate with NMO disease activity.1,3NMO-Ab have also been observed in some patients with limited forms of the disease (NMO spectrum disorders), including longitudinally extensive transverse myelitis (LETM) and isolated optic neuritis. Studies have demonstrated that injection of NMO-Ab-positive serum into animals or cultured cells expressing AQP4 produces a disruption of the blood-brain barrier, impairment of glutamate homeostasis, and induction of necrotic cell death.3These studies suggest a direct role of NMO-Ab in the pathogenesis of NMO.Immunoassays employing a variety of different immunological techniques for the detection of NMO-Ab in patients with NMO have been described.3Wingerchuk and associates have proposed a set of criteria for the diagnosis of neuromyelitis optica that incorporate the assessment of NMO-Ab status.7This guideline suggests that the diagnosis of NMO requires two absolute criteria (optic neuritis and acute myelitis) plus at least two of three supportive criteria, one of which is NMO-Ab seropositive status. Measurement of NMO-Ab can be of value in distinguishing NMO from MS when full clinical features may not be apparent and early intervention may prevent or delay disability. Early diagnosis of NMO is critical for avoiding the cumulative effects that result in progressive disability. A positive value is consistent with NMO or a related disorder and helps justify initiation of appropriate therapy.Four hundred thirty-three samples routinely submitted for NMO-Ab testing were tested by both the aquaporin-4 autoantibody ELISA and indirect immunofluorescence assay (IFA) performed at Mayo Clinic Laboratory.898.1% of results were in agreement with a positive result agreement of 78.6% and negative result agreement of 98.8% (IFA as reference method). These results are comparable to those observed in a previously published study comparing an ELISA to IFA for diagnosing NMO.9

Autoimmune & Inflammation

Offered as part of multiple lab tests

Autoimmune & Inflammation, Infectious Diseases

Offered as part of multiple lab tests

Diabetes & Blood Sugar, Autoimmune & Inflammation

Offered as part of multiple lab tests

Diabetes & Blood Sugar, Autoimmune & Inflammation

Offered as part of multiple lab tests

Autoimmune & Inflammation

This panel supports the evaluation of systemic lupus erythematosus (SLE) and related autoimmune diseases, such as mixed connective tissue disease, systemic sclerosis, and Sjogren syndrome. However, testing for subserologies in the absence of a positive antinuclear antibody (ANA) result and clinically suspected autoimmune disease is generally not recommended [1].This panel simultaneously tests for ANAs with an immunofluorescence assay (IFA) and 6 specific autoantibodies associated rheumatic and related diseases. The ANA testing has high sensitivity (97%) for SLE but limited specificity (34%) [2]. Thus, a positive ANA test result does not exclude other autoimmune diseases with similar clinical features [3]. Testing for specific autoantibodies, as well as other biomarkers associated with these autoimmune diseases, in a panel may expedite the evaluation of SLE.Although individuals with negative results on the ANA IFA usually also have negative results for specific ANAs, Jo-1 antibody may be detected in ANA IFA-negative patients with some types of myositis, and SSA antibody may be detected in some ANA IFA-negative patients with lupus or Sjogren syndrome [1].The results of this test should be interpreted in the context of pertinent clinical and family history and physical examination findings.References1. Yazdany J, et al.Arthritis Care Res (Hoboken). 2013;65(3):329-339.2. Petri M, et al.Arthritis Rheum. 2012;64(8):2677-2686.3. Kavanaugh A, et al.Arch Pathol Lab Med. 2000;124(1):71-81.

Autoimmune & Inflammation, Blood Disorders

Monoclonal antibody-based therapies block available CD20-binding sites and, therefore, the antibody used for this flow cytometric assay cannot recognize the CD20 molecule on B cells. The concomitant use of the CD19 marker provides information on the extent of B-cell depletion when using this particular treatment strategy. This Flow Cytometry panel is also useful for confirming the complete absence of B cells in suspected primary humoral immunodeficiencies.

Mental Health & Neurological, Autoimmune & Inflammation

Offered as part of multiple lab tests

Autoimmune & Inflammation, Mental Health & Neurological

Myasthenia gravis (MG) is a chronic, autoimmune disease of the motor system characterized by fatigable weakness with sensory and autonomic sparing.MG is caused by autoantibodies against proteins of the neuromuscular junction. Most cases of generalized MG are anti-acetylcholine receptor (AChR) antibodypositive; a sub-fraction of MG patients produce antibodies against Muscle Specific receptor tyrosine Kinase (MuSK).Of generalized MG patients who lack anti-AChR antibodies (AChR-seronegative), about 40% are positive for Muscle-Specific Kinase (MuSK) antibody.MuSK MG accounts for 5-8% of all MG and is characterized by prominent facial, bulbar and respiratory weakness, frequent respiratory crises, and atrophy of the tongue and masseter muscles.MuSK antibody levels have been shown to correlate with disease severity. Serial measurements may be useful to follow treatment.

Autoimmune & Inflammation, Mental Health & Neurological

Myasthenia gravis (MG) is a chronic, autoimmune disease of the motor system characterized by fatigable weakness with sensory and autonomic sparing.MG is caused by autoantibodies against proteins of the neuromuscular junction. Most cases of generalized MG are anti-acetylcholine receptor (AChR) antibodypositive; a sub-fraction of MG patients produce antibodies against Muscle Specific receptor tyrosine Kinase (MuSK).Of generalized MG patients who lack anti-AChR antibodies (AChR-seronegative), about 40% are positive for Muscle-Specific Kinase (MuSK) antibody.MuSK MG accounts for 5-8% of all MG and is characterized by prominent facial, bulbar and respiratory weakness, frequent respiratory crises, and atrophy of the tongue and masseter muscles.MuSK antibody levels have been shown to correlate with disease severity. Serial measurements may be useful to follow treatment.

Autoimmune & Inflammation, Bone Health

Offered as part of multiple lab tests

Autoimmune & Inflammation

Scleroderma Profile Interpretation• Anti-Nuclear Abs: Positive in more than 95% of patients with Scleroderma.• Anti-Centromere Abs are found in more than 95% of patients with Scleroderma.• Anti-Centromere Abs are found in 46% of patients with limited Systemic Sclerosis and 11% in diffuse Systemic Sclerosis, as well as 12% of patients with primary biliary cirrhosis, and are rarely present in normal individuals. The antibodies recognize primarily Centromere B, a major centromere protein, and are associated with CREST Syndrome.• Anti-Scl 70 are highly specific for scleroderma. They are present in about 20% of diffuse SSc, and 10% of limited SSc. The antibodies are associated with digital ulcers, Raynaulds, pulmonary fibrosis, renal crises, and heart disease. EIA testing can yield false positive results, therefore, all EIA positive tests are confirmed with immunodiffusion.• Anti-U1 RNP abs can be found in 2-14% of limited SSc and 5% of diffuse SSc, They are associated with isolated pulmonary arterial hypertension, arthritis, and esophageal dysfunction.• Anti-TH/TO abs can be found in 2-6% of patients with limited SSc and are rarely found in diffuse SSc. They are associated with isolated pulmonary arterial hypertension, arthritis, and esophageal dysfunction.• Anti-Fibrillarin (U3 RNP) are highly specific for diffuse SSc with a sensitivity of 4-10%. They are associated with isolated arterial hypertension, myositis, and cardiac manifestations of SSc.• Anti-RNA Polymerase III are useful in the diagnosis of SSc and for the identification of patients at risk for developing renal crisis, progressive skin thickening and cancer. The prevalence of IgG RNAP III antibodies is 20-30% in diffuse SSc and 9% in limited SSc.

Mental Health & Neurological, Autoimmune & Inflammation

Offered as part of multiple lab tests

Autoimmune & Inflammation

Offered as part of multiple lab tests

Mental Health & Neurological, Autoimmune & Inflammation

Neuromyelitis optica spectrum disorders (NMOSDs), classified as immune-mediated chronic and frequently recurring inflammatory conditions, primarily impact the optic nerve and spinal cord. While NMOSDs can occur in any demographic, they tend to be more prevalent in middle-aged and elderly women. Due to the presence of similar symptoms such as optic neuritis and transverse myelitis, NMOSDs are sometimes misdiagnosed as multiple sclerosis (MS). However, distinguishing factors between the two conditions include the clinical progression, the location and size of lesions in the brain and/or spinal cord, the occurence of optic neuritis, and the detection of specific autoantibodies like aquaporin-4 receptor (AQP4) or myelin oligodendrocyte glycoprotein (MOG) IgG. Once initial non-specific tests have been conducted to exclude infections, vasculitis and other conditions that may resemble NMOSDs in their presentation, it is recommended to assess the serum antibody status for AQP4 IgG and MOG IgG. The detection of AQP4 IgG antibodies in the appropriated clinical context confirms the presence of NMOSDs. In patients with MS, AQP4 IgG testing generally yields negative results, whereas around 75% of NMOSD patients show antibodies targeting the AQP4 receptor. Although a small percentage of individuals with clinical symptoms suggestive of NMOSDs may test negative for AQP4 IgG, they may still have detectable serum MOG IgG antibodies. It is important to note that the absence of both AQP4 IgG and MOG IgG antibodies does not exclude the diagnosis of NMOSD, and it is advisable to consider retesting before initiating antibody-targeted therapies.