title: Celiac disease: Autoimmunity in response to food antigen.
abstract: Celiac disease (CD) is an increasingly common disease of the small intestine that occurs in genetically susceptible subjects by ingestion of cereal gluten proteins. Gluten is highly abundant in the modern diet and well tolerated by most individuals. In CD, however, an erroneous but highly specific, adaptive immune response is mounted toward certain parts of the gluten proteome. The resulting intestinal destruction is reversible and resolved upon removal of gluten from the diet. Post-translational modification (deamidation) of gluten peptides by transglutaminase 2 (TG2) is essential for the peptides to act as HLA-DQ-restricted T-cell antigens. Characteristically, deamidated gluten and the self-protein TG2 both become targets of highly disease specific B-cell responses. These antibodies share several peculiar characteristics despite being directed against vastly different antigens, which suggests a common mechanism of development. Importantly, no clear function has been ascribed to the antibodies and their contribution to disease may relate to their function as antigen receptors of the B cells rather than as soluble immunoglobulins. Adaptive immunity against gluten and TG2 appears not to be sufficient for establishment of the disease lesion, and it has been suggested that stress responses in the intestinal epithelium are essential for the development of full-blown disease and tissue damage. In this review we will summarize current concepts of the immune pathology of CD with particular focus on recent advances in our understanding of disease specific B-cell responses.
authors.affiliation: Centre for Immune Regulation and Department of Immunology, University of Oslo and Oslo University Hospital, Oslo, Norway. Electronic address: jorunn.stamnas@medisin.uio.no.
authors.forename: J
authors.initials: J
authors.lastname: Stamnaes
authors.affiliation: Centre for Immune Regulation and Department of Immunology, University of Oslo and Oslo University Hospital, Oslo, Norway. Electronic address: l.m.sollid@medisin.uio.no.
authors.forename: L M
authors.initials: LM
authors.lastname: Sollid
mesh_terms: D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D000941:Antigens / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002446:Celiac Disease / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology* / Q000378:metabolism; D005502:Food / Q000009:adverse effects*; D019204:GTP-Binding Proteins / Q000276:immunology; D020022:Genetic Predisposition to Disease; D005983:Glutens / Q000009:adverse effects; D006683:HLA-DQ Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D011503:Transglutaminases / Q000276:immunology
chemical_list: D000941:Antigens; D001323:Autoantibodies; D001324:Autoantigens; D006683:HLA-DQ Antigens; D005983:Glutens; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins
keywords: Autoimmunity; B cells; Celiac disease; Gluten; HLA; T cells