Serological Markers of Celiac Disease

Serological testing for autoantibodies relevant to CD includes measurement of antigliadin antibodies (AGA), serum endomysial antibodies (EMA), tissue transglutaminase antibodies (tTG), and total serum IgA. Antigliadin antibodies are antibodies against the proteins present in the ethanol-soluble fraction of wheat gluten and can be measured using IgA- or IgG-specific AGA ELISA assays. The AGA test is the least sensitive (IgA AGA 75-90%; IgG AGA 69-85%) and least specific (IgA AGA 82-95%; IgG AGA 73-90%) serological test for the diagnosis of CD.2 The lower sensitivity of AGA

is illustrated in this patient's lab results, where AGA IgA and IgG were both negative, even though the other serological tests for CD were positive and the diagnosis of CD was confirmed by biopsy and response to a gluten-free diet.

IgA EMA are detected by indirect immunofluorescence using monkey esophagus or human umbilical cord frozen sections as substrate, and results are expressed as titers. Traditionally EMA was the preferred serological test for CD with the highest sensitivity (85-98%) and specificity (97-100%);2 however, indirect IF is considered a laborintensive, observer-dependent method. In 1997, it was shown that tTG is the autoantigen of endomysial antibodies, and ELISA assays for anti-tTG antibodies were developed.6 IgA tTG antibodies are more sensitive (90-98%) than EMA and have similar specificity (94-97%).2 Sensitivity and specificity variation are due to differences in methodology and the source of tTG (guinea pig or human recombinant). Approximately 2% of patients with the diagnosis of CD are IgA-deficient, which is a 10-16-fold higher occurrence than observed in the general population.7 IgA deficiency in patients with CD often leads to negative ser-ological test results in assays using anti-IgA antibodies. It is often useful to measure total serum IgA as part of the diagnostic workup for celiac disease, especially when IgA-based serology assays are being utilized.

The role of serological testing in the diagnosis of CD includes identification of patients for whom biopsy might be warranted because of the presence of characteristic symptoms, or because they are at increased risk for CD due to the presence of associated disorders. Once CD is biopsy-confirmed, serological tests may be used to monitor dietary compliance since they are seldom detectable 6-12 months after the introduction of a gluten-free diet. Further studies and improvements in methodology may allow serological testing to be used for screening of the general population and/or may eliminate the need for biopsy.

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