PT  - JOURNAL ARTICLE
AU  - B Wesche
AU  - E Jaeckel
AU  - C Trautwein
AU  - H Wedemeyer
AU  - A Falorni
AU  - H Frank
AU  - A von zur Mühlen
AU  - M-P Manns
AU  - G Brabant
TI  - Induction of autoantibodies to the adrenal cortex and pancreatic islet cells by interferon alpha therapy for chronic hepatitis C
AID  - 10.1136/gut.48.3.378
DP  - 2001 Mar 01
TA  - Gut
PG  - 378--383
VI  - 48
IP  - 3
4099  - http://gut.bmj.com/content/48/3/378.short
4100  - http://gut.bmj.com/content/48/3/378.full
SO  - Gut2001 Mar 01; 48
AB  - BACKGROUND/AIMS Interferon alpha (IFN-α) therapy for chronic hepatitis C may trigger induction of autoimmunity against several organs. Immune reactions against distinct adrenocortical protein antigens involved in adrenal autoimmune disease have not been reported to date. Therefore, we investigated the development of highly sensitive and specific adrenal autoantibodies in patients with chronic hepatitis C in response to IFN-α treatment. In addition, we studied induction of pancreatic islet and thyroid autoantibodies.PATIENTS/METHODS Sera of 75 patients (42 males, 33 females; mean age 47 (13) years) were analysed before, during, and after IFN-α therapy (9–18×106 IE/week; mean duration 8.3 (3.5) months). Autoantibodies (Abs) to adrenal 21-hydroxylase (21OH-Abs), and to islet glutamic acid decarboxylase (GAD65-Abs) and protein tyrosine phosphatase (IA2-Abs) were determined by a radiobinding assay using35S labelled protein generated by an in vitro translation system. Thyroid antibodies were measured by a commercially available ELISA.RESULTS Thirteen of 75 patients were initially positive for some of the autoantibodies. During or after IFN-α therapy, 3/62 initially negative patients (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 developed diabetes mellitus or impaired glucose tolerance.CONCLUSIONS IFN-α induces 21OH-Abs in some cases, while islet and thyroid specific autoantibodies are more frequently found. However, our results indicate for the first time that the adrenal cortex also has to be considered as a potential target of IFN-α related autoimmunity.AbsantibodiesACAadrenal cortex antibodiesACTHcorticotrophinANAantinuclear antibodiesGAD65glutamic acid decarboxylaseHCVhepatitis C virusIA2protein tyrosine phosphataseIAAinsulin autoantibodiesIDDMinsulin dependent diabetes mellitusIGTimpaired glucose toleranceIFN-αinterferon alphaLKMliver-kidney microsomal antibodiesNIDDMnon-insulin dependent diabetes mellitus21OH21-hydroxylaseTGthyroglobulinTPOthyroid peroxidase