Deamidated gliadin peptides from epitopes that transglutaminase antibodies recognize?

KORPONAY-SZABO, I; VECSEI, Z; KIRALY, R; DAHLBOM, I; CHIRDO, FG; NEMES, E; FESUS, L; MAKI, M

JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION

Philadelphia, USA

Lugar: Lippincott Williams & Wilkins,; Año: 2008 vol. 46 p. 253 - 261

0277-2116

Objective: Deamidated gliadin peptides are more efficient antigens in diagnostic tests for celiac disease than native gliadin sequences. We investigated whether deamidated gliadin antigens are structurally similar to transglutaminase 2 or could mimic transglutaminase epitopes. Methods: Serum samples from 74 celiac and 65 control patients, and 13 different transglutaminase 2-specific monoclonal mouse antibodies were investigated for their binding to commercially available deamidated gliadin peptides using enzyme-linked immunosorbent assay (ELISA), competition studies and molecular modelling. Results: The ELISA with deamidated gliadin peptide antigens had 100% sensitivity and 98.5% specificity for celiac disease in patients. Deamidated gliadin epitopes were also recognized by three transglutaminase-specific monoclonal antibodies, and antibodies affinity-purified with deamidated gliadin peptides from celiac patient sera reacted with transglutaminase but did not show endomysial binding. The binding of the monoclonal antibodies to deamidated gliadin was inhibited in a dose-dependent manner by full-length recombinant human transglutaminase, its fragments containing the binding sites of these monoclonal antibodies or by celiac patient antibodies. Deamidated gliadin peptides decreased the binding of transglutaminase-specific monoclonal antibodies to transglutaminase. Three different cross-reacting transglutaminase epitopes were found of which two are located in the C-terminal domain and one is conformational. The binding of celiac serum samples to deamidated gliadin peptides could not be abolished by transglutaminase or by any of the transglutaminase-specific monoclonals, indicating that celiac sera also contain additional antibodies to gliadin epitopes different from transglutaminase. Conclusions: Certain deamidated gliadin-derived peptides and transglutaminase 2 epitopes have similar three-dimensional appearance. This homology may contribute to the induction of transglutaminase autoantibodies by molecular mimicry.