Identification and characterization of glima 38, a glycosylated islet cell membrane antigen, which together with GAD(65) and IA2 marks the early phases of autoimmune response in type 1 diabetes

Immunoprecipitating IgG autoantibodies to glutamic acid decarboxylase, GAD(65), and/or a tyrosine phosphatase, IA2, are present in the majority of individuals experiencing pancreatic beta cell destruction and development of type 1 diabetes, Here we identify a third islet cell autoantigen, a novel 38-kD protein, which is specifically immunoprecipitated with sera from a subset of prediabetic individuals and newly diagnosed type 1 diabetic patients. The 38-kD autoantigen, named glima 38, is an amphiphilic membrane glycoprotein, specifically expressed in islet and neuronal cell lines, and thus shares the neuroendocrine expression patterns of GAD(65) and IA2. Removal of N-Linked carbohydrates results in a protein of 22,000 M(r) Glima 38 autoantibodies were detected in 16/86 (19%) of newly diagnosed patients, including three very young children, who had a rapid onset of disease, and in 6/44 (14%) of prediabetic individuals up to several pears before clinical onset. The cumulative incidence of GAD(65) and glima 38 antibodies in these two groups was 83 and 80%, respectively, and the cumulative incidence of GAD(65), glima 38, and IA2 antibodies in the same groups was 91 and 84%, respectively. GAD(65), IA2, and glima 38 represent three distinct targets of immunoprecipitating IgG autoantibodies associated with beta cell destruction and type 1 diabetes.