Start Date
Expiration Date
CPT Codes
Reference Test
ATLAS Test Code

Specimen Information


Gold, SST


0.5 ml

Transport Info


Fasting Required?
Patient Instructions

Reference Range

0.0-7.0 U/mL


Enzyme-Linked Immunosorbant Assay (ELISA)

Clinical Significance

Celiac disease and dermatitis herpetiformis, the two recognized forms of gluten-sensitive enteropathy (GSE), are characterized by chronic inflammation of the intestinal mucosa and flattening of the epithelium or positive "villous atrophy". Intolerance to gluten, the protein of wheat, rye, and barley, causes GSE. Patients with celiac disease may suffer from diarrhea, gastrointestinal problems, anemia, fatigue, psychiatric problems, and other diverse side effects or they may be asymptomatic. Dermatitis herpetiformis is a skin disease associated with GSE. All GSE patients have an increased risk of lymphoma. A gluten-free diet controls GSE and associated risks. The finding in the 1950s that gluten causes celiac disease made treatment possible by placing patients on a gluten-free diet. After the development of a method for taking small bowel biopsies orally, physicians were able to check for villous atrophy. While villous atrophy may occur in other disorders, GSE can be proven by following the original criteria of the European Society for Pediatric Gastroenterology and Nutrition (ESPGAN). These criteria call for approximately a year of arduous studies with: a) an initial positive gut biopsy, b) six months on a gluten- free diet, c) a negative second gut biopsy, d) a gluten challenge for six months, and e) a positive third gut biopsy. The development of serum tests for three different antibodies of the IgA isotype made it possible to generate more rapid, revised ESPGAN criteria for celiac disease as reported in 1990. These tests include IgA endomysial antibodies (EMA), IgA anti-gliadin antibodies (AGA), and R1 anti-reticulin antibodies (ARA). The revised ESPGAN criteria call for: a) a single positive gut biopsy and b) the demonstration of at least two of the three IgA class antibodies mentioned above. Since then, several studies have demonstrated that IgA EMA tests have over 99 percent specificity for GSE and a greater sensitivity than ARA or AGA tests. Since the IgA EMA disappear when patients with celiac disease or dermatitis herpetiformis adhere to a gluten-free diet, tests for these antibodies also aid in checking on the adherence of patients to their diet. Recently, the endomysial antigen has been identified as the protein cross-linking enzyme known as tissue transglutaminase (tTG). Antigen-specific ELISA procedures incorporating tTG afford a reliable, objective alternative to the traditional immunofluorescent-based assays incorporating thin sections of primate esophagus as substrate. The ELISA procedure can be adapted to both large and small numbers of patient samples. Within the last two years the human tTG antigen has been produced by recombinant technology. Recombinant human antigen may have certain advantages compared with the more traditional guinea pig liver antigen. Two more recent developments in celiac disease serology are the use of native human tissue transglu-taminase isolated from red blood cells and the use of tests capable of detecting IgG class tissue transglutaminase. Use of native human red blood cell tTG rather than guinea pig or recombinantly derived human antigen eases purification and results in preparations free from bacterial, insect, or other contaminating proteins. The human antigen tTG ELISA assays that are presented in the literature appear to work well in comparison to the more traditional guinea pig antigen-based tests. A common problem encountered when testing patients for celiac disease by serological means is that it is not uncommon for celiac patients to be IgA deficient. This IgA deficiency is probably the single largest contributor to a false negative serological result in biopsy-confirmed celiac patients. To compensate, many laboratories perform IgG determinations of several commonly tested for celiac antibodies, such as reticulin and gliadin. Most IgA-deficient celiac patients are found to be positive for IgG class reticulin and gliadin. Several groups have published on using an IgG version of the tTG assay to pick up IgA-deficient GSE patients. In one study, test sensitivity was increased from 91.5 percent for IgA antibody alone to 98.5 percent when both IgA and IgG results were considered. The h-tTG IgG assay may be used to rule out or aid in the diagnosis of GSE in patients who are IgA deficient. Test results alone are not diagnostic. Results should be used in conjunction with other clinical findings to make a diagnosis of a gluten-sensitive enteropathy.