Celiac Disease Serology

2003, Volume 14, Number 1


Richard S. Bak, Ph.D.

Celiac disease is an inflammatory condition of the small intestine. The inflammation is brought about, in genetically predisposed individuals, by the ingestion of a protein called gluten which is contained in wheat, rye, and barley. This disease, also called Celiac Sprue or Gluten Sensitive Enteropathy may occur at any time in life, but begins most often in infancy after gluten containing cereals are introduced into the diet. The resulting inflammation causes malabsorption of nutrients, fluids, and electrolytes. An individual suffering from Celiac Disease may experience quite severe diarrhea, weakness, and weight loss.

Gluten sensitivity can also affect the skin and this condition is called dermatitis herpetiformis (DH). Patients with DH often present with a burning, blistering rash on the buttocks and extensor surfaces of the body.

Patients with celiac disease produce antibodies against several substances, including endomysium (EMA), gliadin (anti-gliadin antibodies, AGA), tissue transglutaminase (tTG), and reticulin. IgA antibodies usually predominate but because about 1 in 300 individuals are IgA deficient, screening tests should include at least one IgG assay (e.g. IgG anti-gliadin).

The gold standard for confirming celiac disease is a biopsy specimen that demonstrates the characteristic inflammatory lesions in the lining of the small intestine and a clinical response to a gluten-free diet.



Endomysial antibodies are recognized as the best serological screening test for celiac disease [1-4] and also the best serological marker of Gluten Sensitive Enteropathy in patients with DH [5]. However the test requires microscopic interpretation of immunoflourescent staining.

IgA and IgG gliadin antibodies are found in many untreated patients with celiac disease. Measurement of anti-gliadin antibodies has been well standardized. The IgA antibodies are particularly useful for monitoring adherence to a gluten-free diet. The IgG antibodies are useful for screening patients with IgA deficiency. Because most IgA deficient patients have no symptoms of that deficiency, if only IgA tests are used to screen for celiac disease, those cases will be missed.

Tissue Tranglutaminase antibodies are directed against the primary antigenic components of endomysium. The tissue transglutaminase assays have been reported, by various investigators, to have a sensitivity of 95 to 98% for the detection of celiac disease [6].

Reticulin antibodies are no longer considered useful in the diagnosis of celiac disease. They lack the sensitivity and specificity of the endomysial antibody and tissue tranglutaminase assays.



Celiac disease is much more common than was realized prior to the advent of serological testing. It occurs with a prevalence rate of two to twelve per 1,000 persons in the general population. It occurs at higher rates in persons with dermatitis herpetiformis, lymphocytic colitis, short stature, Down’s syndrome, Turner’s syndrome, selective serum IgA deficiency, primary biliary cirrhosis, type 1 diabetes mellitus, autoimmune thyroid disease, and epilepsy [7].

Celiac disease may present asymptomatically in up to one-third of cases, or it may present with a variety of different symptoms and signs, many of which are not gastrointestinal. Among a primary care population, undiagnosed celiac disease occurred in one of eight patients presenting with anemia, one in fifty patients presenting with fatigue, and one of fifty patients presenting with irritable bowel syndrome [8].

In suspected cases of celiac disease, which test or combination of tests is optimum? Experts in the field have differing opinions. Researchers at the Mayo Clinic found that initial screening with EMA was the most cost-effective strategy for diagnosing celiac disease in low-risk populations while initial screening with the gliadins was the most cost-effective strategy for higher risk groups. [9] The researchers, however, did not examine the cost-effectiveness of tissue transglutaminase.

Fasano and Catassi [10] recommend tissue transglutaminase as the initial screen as do Carroccio et al. [11] provided that one uses the newer human tissue transglutaminase assay rather than the original guinea pig assay. Kumar et al. [12] recommends tissue transglutaminase or anti-gliadins plus endomysial antibodies as the preferred initial screen.

Two groups have published criteria or guidelines for diagnosing celiac disease. The criteria of the European Society for Pediatric Gastroenterology calls for positive results in two of the serological tests confirmed by a single biopsy [13]. The Delaware Medical Society has recently recommended initial screening with anti-gliadin IgA, anti-gliadin IgG, and endomysial IgA tests [7]. We agree with this recommendation because all IgA deficient patients would be missed unless an IgG assay is used. Positive results should be followed by small bowel biopsy for confirmation.



Celiac disease is believed to be an underdiagnosed disease in the United States. Serologic testing, particularly endomysial antibody testing, is highly sensitive and specific for celiac disease and provides a rapid means of identifying those patients who should be biopsied.

Sensitivity and Specificity of Serologic Tests for Celiac Disease.
IgA anti-endomysial antibody85-9897-100
IgA anti-tissue transglutaminase (ELISA)95-9894-95
IgA anti-gliadin75-9082-95
IgG anti-gliadin69-8573-90
Data from Farrell and Kelly (Farrell, R. J. and C. P. Kelly (2002. “Celiac sprue.” N Engl J Med 346(3): 180-8.)



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