1178-P: Autoantibodies Specifically Targeting Oxidative Post-translationally Modified Insulin in Type 1 Diabetes

Introduction & Objective: Antibodies to oxidative post-translational modifications of insulin (oxIAA) have been reported in patients with type 1 diabetes (T1D). The specificity of oxIAA related with natural insulin autoantibodies (IAA) is yet to be established.

Methods: Oxidized insulin (•OH-INS) was generated by exposing insulin to hydroxyl radical. The method for detecting autoantibodies to •OH-INS (oxIAA) in the present study used an electrochemiluminescence (ECL) assay as previously used for IAA. In total, 539 samples were tested including 254 from healthy children negative for all islet autoantibodies and 285 from T1D patients newly diagnosed within 2 weeks. Radio-binding assays were performed for all islet autoantibodies (IAA, GADA, IA-2A and ZnT8A) for all participants. Absorption assays for oxIAA were performed using both insulin and OH-INS.

Results: With the specificity set at 95% of 254 controls, the sensitivity of oxIAA was 16.8% (48/285) in patients with new-onset T1D. Of 48 positives for oxIAA, 31 were IAA positive and 17 were IAA negative. Eight sera positive for oxIAA from T1D patients were randomly selected for absorption assay including 4 positive for both oxIAA and IAA, and 4 positive only for oxIAA. The oxIAA from all 8 sera studied were able to be completely absorbed by •OH-INS while the absorption by insulin were poor, showing partial absorption.

Conclusion: Autoantibodies targeting oxidative post-translationally modified insulin can be detected in patients with new onset T1D. The present data that the oxIAA were present in IAA-negative patients and oxIAA were absorbed by •OH-INS, better than natural insulin, demonstrated that oxIAA (specifically against •OH-INS) are novel antibodies in T1D. Further study in pre-T1D subjects will be focused on oxIAA as new risk biomarker of T1D development.