Distinct idiotypes of insulin autoantibody in autoimmune polyendocrine syndrome type 2 and childhood onset type 1 diabetes

Insulin autoantibodies (IAA) are present in type 1 diabetes (T1D) and other autoimmune diseases. The differences in the IAA epitopes in various clinical diseases have not been evaluated. We used phage display to select phagotopes specific to IAA from a newly diagnosed T1D child ( designated FPP) and from an adult-onset T1D subject with autoimmune polyendocrine syndrome type 2 (APS-II). The phagotopes randomly selected were tested as antiidiotope reagents to displace human radiolabeled insulin in the microfiltration radiobinding assay using IAA(+) sera from T1D subjects and insulin antibody (IA(+)) sera from insulin-treated type 2 diabetes subjects. The DNA of the phagotopes selected from the FPP and APS sera revealed consensus amino acid sequences of GRG and LGKRS, respectively. Phagotope FPP-10 displaced insulin binding in 90% of IAA(+) subjects but not in the IA(+) or the APS subject. Phagotope APS-4 was able to displace insulin binding from the APS subject but not in the IAA(+) or IA(+) subjects. We have demonstrated antiidiotope reagents able to distinguish childhood-onset T1D-associated IAA(+) from adult-onset T1D (APS-II-associated IAA(+)) that are different from their specificity for human insulin and from its antiidiotope amino acid sequence.