Two Distinct Glutamic Acid Decarboxylase Auto-Antibody Specificities in IDDM Target Different Epitopes

摘要: Although most individuals with insulin-dependent diabetes mellitus (IDDM) have autoantibodies to glutamic acid decarboxylase (GAD), antibodies GAD are also present in some a low risk of developing diabetes. The IDDM specific for the 65 isoform, do not bind denatured protein, and target epitope(s) dependent on conformation protein. However, epitopes been difficult further define because protein fragments or synthetic peptides. Since 67 isoform is highly homologous but usually sera, we created six /GAD chimeric proteins maintain overall used these map conformation-dependent targeted by sera. We find that binding sera ( n = 11 12) composed two distinct antibody specificities different regions one located between amino acids 240 435 (termed IDDM-E1) 451 570 IDDM-E2). One DDDM serum (it 1 bound only IDDM-E1 region. Identification may allow distinguish antibody-positive at high determine if differences autoimmune repertoire directed present. be useful designing assays IDDM.