Interferon‐B Anti‐viral Therapy Induced Type II Diabetes

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Studies have shown that extensive interferon treatment can trigger autoimmune disorders such as thyroiditis, systemic lupus erythematosus and diabetes. In all cases, patients exhibited no preexisting autoimmunity, suggesting that the induction of auto-reactive antibodies (Ab) was a result of the immunosuppressive therapy. In this study, we investigated the molecular events which may have lead to the development of insulin resistance in a 55 year-old African American male diagnosed with insulin-dependent type II diabetes after a 35 week treatment with polyethylene glycol (PEG) interferon/ribavirin therapy for hepatitis C virus. Patient serum and sera from healthy human male donors were tested for the presence of Abs reactive against human insulin receptor (hIR). Insulin receptor-specific Abs were monitored by immunoprecipitation and Western blotting lysates from Chinese Hamster Ovary (CHO) cells lacking or expressing the human receptor (the latter CHO/IR membrane fragments). While patient serum was not reactive with membrane fraction of CHO/IR cells on Western blots, the hIR from CHO/IR, the serum immunoprecipitated the hIR from CHO/IR membrane fragments such that IR was detected with commercial Abs insulin receptor-alpha and insulin receptor-beta subunits. We are currently, in the process of testing whether these Abs are capable of disrupting IR function in vitro and our results indicated that the patient has developed antibodies against his insulin receptors. Supported in part by NIGMS Grant No. GM067592.