Deamidated gliadin peptides as targets for celiac disease-specific antibodies.
Celiac disease (CD) is an (auto)immunologically mediated intestinal intolerance against proteins from wheat (gluten) and related cereal proteins. Tissue transglutaminase (tTG) has been identified as the autoantigen in CD. Although ultimate diagnosis is based on histological analysis of small intestinal mucosa obtained via tissue biopsy, assessment of autoantibodies can provide substantial help in the evaluation of CD. Gliadin antibodies are directed against the native disease-provoking cereal proteins. Despite their initial usefulness, these antibodies have lost diagnostic importance due to their poor specificity and sensitivity as CD markers. Recently, it was found, however, that gliadin antibodies from sera of patients with active CD preferentially recognized deamidated gliadin peptides. The use of deamidated gliadin peptides in immunoassays has significantly improved the usefulness of gliadin antibodies in diagnosis of CD to that observed with autoantibody assay methods (endomysium antibodies, antibodies against tTG). The antibody epitopes (B-cell epitopes) reflect substrate specificity of tTG and resemble peptide sequences known to be strongly T-cell stimulatory (T-cell epitopes) in CD. The assay applying deamidated gliadin peptides measures a new species of antibodies, which is different from conventional gliadin antibodies as well as from autoantibodies and will likely provide new information on pathophysiological mechanisms of CD.
Institute for Laboratory Medicine, Clinical Chemistry, and Molecular Diagnostics, University Hospital and Medical Faculty of the University, Leipzig, Germany.
Thomas
T
Mothes
D000906:Antibodies / Q000097:blood* / Q000276:immunology; D000918:Antibody Specificity; D001323:Autoantibodies / Q000097:blood; D002446:Celiac Disease / Q000175:diagnosis* / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D000939:Epitopes / Q000276:immunology; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005903:Gliadin / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D010455:Peptides / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D013379:Substrate Specificity; D011503:Transglutaminases / Q000276:immunology / Q000378:metabolism*
D000906:Antibodies; D001323:Autoantibodies; D000939:Epitopes; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D010455:Peptides; D005903:Gliadin; D011503:Transglutaminases