title: Etiopathogenesis of insulin autoimmunity.
abstract: Autoimmunity against pancreatic islet beta cells is strongly associated with proinsulin, insulin, or both. The insulin autoreactivity is particularly pronounced in children with young age at onset of type 1 diabetes. Possible mechanisms for (pro)insulin autoimmunity may involve beta-cell destruction resulting in proinsulin peptide presentation on HLA-DR-DQ Class II molecules in pancreatic draining lymphnodes. Recent data on proinsulin peptide binding to type 1 diabetes-associated HLA-DQ2 and -DQ8 is reviewed and illustrated by molecular modeling. The importance of the cellular immune reaction involving cytotoxic CD8-positive T cells to kill beta cells through Class I MHC is discussed along with speculations of the possible role of B lymphocytes in presenting the proinsulin autoantigen over and over again through insulin-carrying insulin autoantibodies. In contrast to autoantibodies against other islet autoantigens such as GAD65, IA-2, and ZnT8 transporters, it has not been possible yet to standardize the insulin autoantibody test. As islet autoantibodies predict type 1 diabetes, it is imperative to clarify the mechanisms of insulin autoimmunity.
authors.affiliation: Department of Clinical Sciences, Skåne University Hospital (SUS), Lund University, CRC Ing 72 Building 91:10, 205 02 Malmö, Sweden.
authors.forename: Norio
authors.initials: N
authors.lastname: Kanatsuna
authors.forename: George K
authors.initials: GK
authors.lastname: Papadopoulos
authors.forename: Antonis K
authors.initials: AK
authors.lastname: Moustakas
authors.forename: Ake
authors.initials: A
authors.lastname: Lenmark