Etiopathogenesis of insulin autoimmunity.

Anatomy Research International
Norio KanatsunaAke Lenmark

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.

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Citations

Jun 16, 2015·Scandinavian Journal of Immunology·N KanatsunaÅ Lernmark
Aug 13, 2013·The Journal of Biological Chemistry·Norio KanatsunaÅke Lernmark

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Methods Mentioned

BETA
biopsy
immunoprecipitation
ELISA
genotyping

Software Mentioned

DAISY
DIPP
BABYDIAB

Related Concepts

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