title: IgG anti-tTG responses in different autoimmune conditions differ in their epitope targets and subclass usage.
abstract: Antibodies of the IgA class directed against the enzyme tissue transglutaminase (tTG) are highly specific for coeliac disease (CD). IgG antibodies to tTG also occur in CD, and have also been reported in autoimmune diseases such as type 1 diabetes mellitus and Crohn's disease. In comparison to the IgA anti-tTG response, little is known of the IgG anti-tTG response in terms of epitope specificity and IgG subclass usage. The aim of this study was to investigate and compare epitopes recognised by CD and non-CD IgG anti-tTG antibodies, and determine the relative proportions of the IgG subclasses comprising this response. IgG anti-tTG positive individuals who did not have CD were identified by screening groups of patients with type I diabetes mellitus, Crohn's disease and granulomatosis with polyangiitis. Results from ELISA blocking experiments and mutant tTG antigens demonstrate that non-CD IgG anti-tTG bind different epitopic determinants to CD IgG anti-tTG. The IgG subclass usage of coeliac disease and type 1 diabetes was dominated by IgG1, whereas this IgG subclass was infrequently a component of the IgG anti-tTG response in diseases such as granulomatosis with polyangiitis and Crohn's disease. The differences in epitope specificity and subclass usage of IgG anti-tTG observed between CD and non-CD individuals may be due to the differing mechanisms underlying tTG autoimmunity.
authors.affiliation: National Children's Research Centre, Our Lady's Hospital For Sick Children, Crumlin, Dublin 12, Ireland; Institute of Molecular Medicine, Trinity College Dublin, Dublin 8, Ireland; Department of Immunology, St James's Hospital, Dublin 8, Ireland. Electronic address: comerfor@tcd.ie.
authors.forename: Ross
authors.initials: R
authors.lastname: Comerford
authors.affiliation: National Children's Research Centre, Our Lady's Hospital For Sick Children, Crumlin, Dublin 12, Ireland.
authors.forename: Jacinta
authors.initials: J
authors.lastname: Kelly
authors.affiliation: Institute of Molecular Medicine, Trinity College Dublin, Dublin 8, Ireland; Department of Immunology, St James's Hospital, Dublin 8, Ireland.
authors.forename: Conleth
authors.initials: C
authors.lastname: Feighery
authors.affiliation: Dublin Institute of Technology, Kevin Street, Dublin 8, Ireland.
authors.forename: Greg
authors.initials: G
authors.lastname: Byrne
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000276:immunology; D001327:Autoimmune Diseases / Q000201:enzymology* / Q000276:immunology*; D002446:Celiac Disease / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology*; D005260:Female; D019204:GTP-Binding Proteins / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D050505:Mutant Proteins / Q000378:metabolism; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases / Q000276:immunology*; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D000939:Epitopes; D007074:Immunoglobulin G; D050505:Mutant Proteins; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins
keywords: Autoantibodies; Autoimmunity; Coeliac disease; Granulomatosis with polyangiitis; Tissue transglutaminase; Type 1 diabetes