title: Autoimmune mechanisms in type 1 diabetes.
abstract: Type 1 diabetes (T1D) is perceived as a chronic immune-mediated disease with a subclinical prodromal period characterized by selective loss of insulin-producing beta-cells in the pancreatic islets in genetically susceptible subjects. Autoreactive T cells, both CD4 and CD8 cells, have been implicated as active players in beta-cell destruction. A series of autoantigens have been identified in T1D including insulin, glutamic acid decarboxylase (GAD), the protein tyrosine phosphatase-related islet antigen 2 (IA-2), and most recently the zinc transporter Slc30A8 residing in the insulin secretory granule of the beta-cell. The issue whether there is any primary autoantigen in T1D has remained controversial. Given that there are two major HLA haplotypes conferring disease susceptibility, i.e. the DR3-DQ2 haplotype and the DR4-DQ8 haplotype, one may assume that there will be at least two primary antigens in T1D. The first signs of beta-cell autoimmunity might appear already during the first year of life. Autoantibodies may be considered as markers of an ongoing disease process in the pancreatic islets, and they can be used for prediction of T1D in non-diabetic individuals. Autoantigen-specific T-cell responses have been detected from peripheral blood in both patients with T1D and in unaffected subjects, but a clear discrimination between diabetic and non-diabetic subjects have rarely been seen until recently.
authors.affiliation: Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland. mikael.knip@hus.fi
authors.forename: Mikael
authors.initials: M
authors.lastname: Knip
authors.forename: Heli
authors.initials: H
authors.lastname: Siljander
mesh_terms: D000293:Adolescent; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D001324:Autoantigens / Q000737:chemistry / Q000276:immunology*; D015551:Autoimmunity; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis / Q000276:immunology*; D006801:Humans; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D001323:Autoantibodies; D001324:Autoantigens