title: Induction of autoantibodies to the adrenal cortex and pancreatic islet cells by interferon alpha therapy for chronic hepatitis C.
abstract: OBJECTIVE
  Interferon alpha (IFN-alpha) 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-alpha treatment. In addition, we studied induction of pancreatic islet and thyroid autoantibodies.
  
  
  METHODS
  Sera of 75 patients (42 males, 33 females; mean age 47 (13) years) were analysed before, during, and after IFN-alpha therapy (9-18x10(6) 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 using (35)S 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-alpha 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-alpha 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-alpha related autoimmunity.
authors.affiliation: Department of Clinical Endocrinology, Medizinische Hochschule Hannover, Carl-Neuberg-Str 1, D-30623 Hannover, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Wesche
authors.forename: E
authors.initials: E
authors.lastname: Jaeckel
authors.forename: C
authors.initials: C
authors.lastname: Trautwein
authors.forename: H
authors.initials: H
authors.lastname: Wedemeyer
authors.forename: A
authors.initials: A
authors.lastname: Falorni
authors.forename: H
authors.initials: H
authors.lastname: Frank
authors.forename: A
authors.initials: A
authors.lastname: von zur Mühlen
authors.forename: M P
authors.initials: MP
authors.lastname: Manns
authors.forename: G
authors.initials: G
authors.lastname: Brabant
mesh_terms: D000302:Adrenal Cortex / Q000276:immunology*; D000998:Antiviral Agents / Q000627:therapeutic use*; D001323:Autoantibodies / Q000096:biosynthesis*; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000175:diagnosis / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007515:Islets of Langerhans / Q000276:immunology*; D008297:Male; D008875:Middle Aged
chemical_list: D000998:Antiviral Agents; D001323:Autoantibodies; D016898:Interferon-alpha