Tissue transglutaminase (tTG; IgA) antibody is an excellent first-line marker, with high sensitivity and specificity in untreated individuals. The endomysial antibody (EMA; IgA) assay has high specificity for celiac disease and is used to confirm positive IgA anti-tTG results. Although this panel tests for EMA only when anti-tTG (IgA) results are positive, EMA testing can be ordered separately if the IgA anti-tTG result is negative but clinical suspicion remains high. Some patients with limited villous atrophy have been reported to lack EMA and tTG antibodies; testing for IgA antigliadin antibody (AGA) may help detect celiac disease in such patients. Total serum IgA is measured to identify selective IgA deficiency, present in about 2% to 10% of celiac disease patients. Such patients would have negative results on IgA anti-tTG and EMA assays but may have positive IgG anti-tTG results.
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.