AUTOIMMUNITY TO GLUTAMIC-ACID DECARBOXYLASE IN INSULIN-DEPENDENT DIABETES

Most individuals produce autoantibodies and autoreactive T lymphocytes but only about 5% of any population develop an autoimmune disease. Or gan specific autoimmune diseases, including insulin-dependent diabetes mellitus (IDDM), tend to target functional elements such as enzymes. A 64 kD protein is a major islet antigen associated with IDDM and at l east part of the antigen complex has been identified as glutamic acid decarboxylase (GAD) which exists as multiple isoforms and both forms a re recognized by diabetes-associated antibodies. About 80% or more of newly diagnosed patients with IDDM have autoantibodies to intact 64 kD and its trypsin-released fragments. These antibodies could be importa nt predictors of subsequent disease in non-diabetic individuals. Strat egies for disease prevention will involve identification of high risk individuals and their treatment with immunomodulation which alters the immune response to critical antigens such as GAD.