Backguound & Aims: Immunoglobulin A (IgA) autoantibodies to endomysium (EMA
) are highly specific and sensitive markers for celiac disease. Recently, w
e identified tissue transglutaminase (tTG) as the major if not sole endomys
ial autoantigen. Methods: An enzyme-linked immunosorbent assay (ELISA) was
established to measure IgA anti-tTG titers in serum samples from 106 celiac
patients with partial or subtotal villous atrophy, 43 celiac patients on a
gluten-free diet, and 114 diseased and healthy controls. Results were corr
elated with clinical and histological data and with EMA titers. Results: In
patients with biopsy-proven celiac disease consuming a normal, gluten-cont
aining diet, 98.1% of the serum samples had elevated IgA titers against tTG
, whereas 94.7% of the control sera were negative. IgA anti-tTG correlated
positively with semiquantitative IgA EMA titers (r = 0.862; P < 0.0001). Co
nclusions: An ELISA based on tTG allows diagnosis of celiac disease with a
high sensitivity and specificity. IgA anti-tTG and IgA EMA show an excellen
t correlation, further confirming the enzyme as the celiac disease autoanti
gen. Because the assay is quantitative, not subjected to interobserver vari
ation, and easy to perform, it will be a useful tool for population screeni
ng of a hitherto underdiagnosed disease.