Etiology of autoimmune (type 1) diabetes

The purpose is to clarify the etiological mechanisms by which beta cells are attacked by virus causing an autoimmune reaction and the appearance of autoantibodies against either insulin (IAA-first) in DR4-DQ8 children or against glutamic acid decarboxylase (GADA-first) in DR3-DQ2 children. While only one autoantibody is slow, the autoimmune pathogenesis eventually destroys the pancreatic islet beta cells resulting in diabetes. The present project in TEDDY is a never returning opportunity to study still active TEDDY children with and without beta cell autoantibodies and relate peripheral blood findings to the prior history of enterovirus infection and triggers in early life and exposures. Prediction of the genetically controlled rapid insulitis in the BB rat allows dissection of MHC controlled beta-cell killing in a way that is not possible in humans.