title: Immunological effects of transglutaminase-treated gluten in coeliac disease.
abstract: Coeliac disease pathogenesis is characterized by an immune response triggered, in genetically predisposed subjects, by ingested gluten and its withdrawal from the diet is the only available therapy. However, enzymatic modification of gluten through the insertion of lysine to avoid antigen presentation could represent a new therapeutical approach for patients. Sixty-six duodenal biopsies from 17 coeliac patients were cultured for 48 h with gluten or enzymatically-modified gluten (treated with human recombinant transglutaminase type 2 or bacterial transglutaminase, with or without lysine). Interferonγ, anti endomisium and anti transglutaminase IgA antibodies, lactate dehydrogenase and transglutaminase activity were measured in the culture medium. Transglutaminase type 2 expression was evaluated on biopsies by immunohistochemistry. Gluten and transglutaminase-treated gluten increased by 13-15 fold interferon γ release, as well as antibodies, transglutaminase activity, and the immunohistochemical expression of transglutaminase type 2. Addition of lysine to the enzymatic modification of gluten normalized interferon γ, antibodies, transglutaminase activity and immunohistochemical expression of transglutaminase type 2. Lactate dehydrogenase did not differ among the studied groups. Enzymatic modification of gluten by transglutaminase plus lysine prevents the immunologic effects on cultured duodenal biopsies from coeliac patients and could be tested as an alternative therapy in coeliac disease.
authors: Center for Prevention and Diagnosis of Coeliac Disease, Fondazione IRCCS Cà Granda-Ospedale Maggiore Policlinico-Milano, Italy. lucelli@yahoo.com
authors: Luca
authors: L
authors: Elli
authors: Leda
authors: L
authors: Roncoroni
authors: Martin
authors: M
authors: Hils
authors: Ralf
authors: R
authors: Pasternack
authors: Donatella
authors: D
authors: Barisani
authors: Claudia
authors: C
authors: Terrani
authors: Valentina
authors: V
authors: Vaira
authors: Stefano
authors: S
authors: Ferrero
authors: Maria Teresa
authors: MT
authors: Bardella
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D002446:Celiac Disease / Q000178:diet therapy* / Q000276:immunology* / Q000473:pathology; D004386:Duodenum / Q000276:immunology / Q000473:pathology; D005260:Female; D019204:GTP-Binding Proteins / Q000276:immunology / Q000378:metabolism; D005983:Glutens / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D008239:Lysine; D008297:Male; D008875:Middle Aged; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases / Q000276:immunology / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D007070:Immunoglobulin A; D005983:Glutens; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins; D008239:Lysine