Etiopathogenesis of Insulin Autoimmunity. (22nd February 2012)

• Record Type: Journal Article
• Authors: Kanatsuna, Norio; Papadopoulos, George K.; Moustakas, Antonis K.; Lenmark, Åke
• Other Names: Huang Ruijin Academic Editor.
• Is Part Of: Anatomy research international. Volume 2012(2012)
• Publication Date: 2012-02-22
• Subjects: Anatomy -- Periodicals; 611.005
• DOI: 10.1155/2012/457546
• Languages: English
• ISSNs: 2090-2743

Abstract

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.