[Augmentation of the immune response to islet cell antigens with development of diabetes mellitus caused by interferon-alpha therapy in chronic hepatitis C].
We report on a 36-year-old patient suffering from chronic hepatitis C. Because of elevated liver enzymes and histology showing chronic inflammation and periportal fibrosis, interferon-alpha (IFN) therapy was started with a dosage of 5 Mio units three times a week. Four months later the patient hat to be hospitalized due to the typical clinical features of a recent onset type 1 diabetes (BG > 300 mg/dl, HbA1c 9.6%, ketonuria). In serum samples prior to and following interferon therapy, we analyzed titers of diabetes-related autoantibodies responding to GAD65 (glutamic acid decarboxylase), IA2c (tyrosine phosphatase) and ICA (islet cell autoantibodies). While ICA were negative before starting therapy, IA2c-antibodies were highly elevated. In contrast. GAD65-antibodies were elevated only slightly over the cut-off of the assay before therapy (controlled by a second different RIA assay) and increased 100 fold during IFN-alpha treatment. Additionally thyroid antibodies appeared. After the end of the IFN therapy, GAD65- and IA2c antibodies remained on high levels and also ICA could now be found. The patient was positive for HLA-DR4. This case supports the hypothesis that IFN-alpha therapy may lead to an augmented autoimmune reaction against islet cell antigens resulting in the development of diabetes mellitus type 1, especially if there are other predisposing factors before IFN treatment. We further discuss the possible involvement of interferon-alpha in the pathogenesis of autoimmune diabetes with reference to recent studies.
Seifarth
C
C
Medizinische Klinik I mit Poliklinik, Friedrich-Alexander-Universität Erlangen.
Benninger
J
J
Böhm
B O
BO
Wiest-Ladenburger
U
U
Hahn
E G
EG
Hensen
J
J
D000328:Adult; D001324:Autoantigens / Q000097:blood*; D001327:Autoimmune Diseases / Q000139:chemically induced* / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced* / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000276:immunology / Q000628:therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects*; D007515:Islets of Langerhans / Q000276:immunology*; D008111:Liver Function Tests; D008297:Male; D011994:Recombinant Proteins
D001324:Autoantigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins