title: Epithelial transport and deamidation of gliadin peptides: a role for coeliac disease patient immunoglobulin A.
abstract: In coeliac disease, the intake of dietary gluten induces small-bowel mucosal damage and the production of immunoglobulin (Ig)A class autoantibodies against transglutaminase 2 (TG2). We examined the effect of coeliac patient IgA on the apical-to-basal passage of gluten-derived gliadin peptides p31-43 and p57-68 in intestinal epithelial cells. We demonstrate that coeliac IgA enhances the passage of gliadin peptides, which could be abolished by inhibition of TG2 enzymatic activity. Moreover, we also found that both the apical and the basal cell culture media containing the immunogenic gliadin peptides were able to induce the proliferation of deamidation-dependent coeliac patient-derived T cells even in the absence of exogenous TG2. Our results suggest that coeliac patient IgA could play a role in the transepithelial passage of gliadin peptides, a process during which they might be deamidated.
authors.affiliation: Paediatric Research Centre, Medical School, University of Tampere, Tampere 33014, Finland. katri.lindfors@uta.fi
authors.forename: T
authors.initials: T
authors.lastname: Rauhavirta
authors.forename: S-W
authors.initials: SW
authors.lastname: Qiao
authors.forename: Z
authors.initials: Z
authors.lastname: Jiang
authors.forename: E
authors.initials: E
authors.lastname: Myrsky
authors.forename: J
authors.initials: J
authors.lastname: Loponen
authors.forename: I R
authors.initials: IR
authors.lastname: Korponay-Szabó
authors.forename: H
authors.initials: H
authors.lastname: Salovaara
authors.forename: J A
authors.initials: JA
authors.lastname: Garcia-Horsman
authors.forename: J
authors.initials: J
authors.lastname: Venäläinen
authors.forename: P T
authors.initials: PT
authors.lastname: Männistö
authors.forename: R
authors.initials: R
authors.lastname: Collighan
authors.forename: A
authors.initials: A
authors.lastname: Mongeot
authors.forename: M
authors.initials: M
authors.lastname: Griffin
authors.forename: M
authors.initials: M
authors.lastname: Mäki
authors.forename: K
authors.initials: K
authors.lastname: Kaukinen
authors.forename: K
authors.initials: K
authors.lastname: Lindfors
mesh_terms: D000577:Amides / Q000378:metabolism; D000595:Amino Acid Sequence; D001323:Autoantibodies / Q000276:immunology / Q000378:metabolism; D018938:Caco-2 Cells; D002446:Celiac Disease / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D005903:Gliadin / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology* / Q000378:metabolism; D007421:Intestine, Small / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D021381:Protein Transport; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D011503:Transglutaminases / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism
chemical_list: D000577:Amides; D001323:Autoantibodies; D004791:Enzyme Inhibitors; D007070:Immunoglobulin A; D010446:Peptide Fragments; C549457:gliadin p31-43; D005903:Gliadin; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins