Induction of autoantibodies to the adrenal cortex and pancreatic islet cells by interferon alpha therapy for chronic hepatitis C

Background/aims-Interferon alpha (IFN-alpha) therapy for chronic hepatitis C may trigger induction of autoimmunity against several organs. Immune reac tions against distinct adrenocortical protein antigens involved in adrenal autoimmune disease have not been reported to date. Therefore, we investigat ed the development of highly sensitive and specific adrenal autoantibodies in patients with chronic hepatitis C in response to IFN-alpha treatment. In addition, we studied induction of pancreatic islet and thyroid autoantibod ies. Patients/methods-Sera of 75 patients (42 males, 33 females; mean age 47 (13 ) years) were analysed before, during, and after IFN-a therapy (9-18x10(6) IE/week; mean duration 8.3 (3.5) months). Autoantibodies (Abs) to adrenal 2 1-hydroxylase (21OH-Abs), and to islet glutamic acid decarboxylase (GAD65-A bs) and protein tyrosine phosphatase (IA2-Abs) were determined by a radiobi nding assay using S-35 labelled protein generated by an in vitro translatio n system. Thyroid antibodies were measured by a commercially available ELIS A. Results-Thirteen of 75 patients were initially positive for some of the aut oantibodies. During or after IFN-a therapy, 3/62 initially negative patient s (4.8%) developed 21OH-Abs. GAD65-Abs or IA2-Abs appeared in 5/62 and 1/62 patients, respectively (9.7% in total). In 12/62 patients (19.4%), thyroid specific antibodies appeared. In none of the 21OH-Ab positive subjects was adrenal dysfunction observed, and no patient with islet autoantibodies dev eloped diabetes mellitus or impaired glucose tolerance. Conclusions-IFN-alpha induces 21OH-Abs in some cases, while islet and thyro id specific autoantibodies are more frequently found. However, our results indicate for the first time that the adrenal cortex also has to be consider ed as a potential target of IFN-alpha related autoimmunity.