Autoimmunity against pancreatic islets and other tissues before and after interferon-α therapy in patients with hepatitis C virus chronic infection

OBJECTIVE - The aim of the study was to investigate the prevalence of clinical and latent autoimmune diseases in Italian patients with hepatitis C virus (HCV) chronic infection before and after treatment with interferon-oc (IFN-alpha). RESEARCH DESIGN AND METHODS - The evidence of clinical autoimmune disease and the presence of autoantibodies were assessed in 70 patients with HCV chronic infection. Autoantibodies to islet cell (ICA), glucagon-producing cells (GCA),parietal cell (PCA), adrenal cortex (ACA), adrenal medulla (AdMA), nuclei (ANA), liver-kidney microsomal (LKM-Ab), mitochondrial, and smooth muscle (SMA) were tested using the classic indirect immunofluorescence technique. Autoantibodies to GAD (GADAb), second islet cell autoantigen (IA2-Ab), and insulin (IAA) were tested by radioimmunoassay, and thyroid microsomal autoantibodies (TMHA) and thyroglobulin autoantibodies (TGHA) were assessed by hemoagglutination test. RESULTS - None of the 70 patients studied showed evidence of clinical disease before treatment with IFN-a. However, 1 (1.4%) patient was positive for ICA, 2 (2.8%) were positive for GCA, 2 (2.8%) for GADAb, 5 (7.1%) for PCA, 2 (2.8%) for ANA, 3 (3.7%) for SMA, 4 (5.7%) for TMHA, and 2 (2.8%) for TGHA. These frequencies were not significantly different when compared with healthy control subjects. There were 29 (41%) patients who were positive for IAA at low titers compared with 2% of the control subjects (significantly different P < 0.0001). ICA titers of one patient positive for ICA/GADAb increased during the IFN-alpha therapy, and the patient developed type 1 diabetes 5 months after the beginning of treatment. IAA levels did not change during the course of treatment, and none of the IAA(+) patients developed diabetes. Thyroid autoantibody titers increased in 3 of the 4 initially positive patients, with 1 patient becoming positive and 2 thyroid antibody-positive patients developing overt hypothyroidism during IFN-alpha treatment. PCA titers increased in 1 of 5 positive patients. Antibodies to other auto-antigens did not change during the course of treatment. CONCLUSIONS - We have not found an increased frequency of clinical or latent autoimmune diseases in patients with chronic HCV infection. However, this study suggests that screening patients for autoantibodies tin particular thyroid and pancreas) before and during IFN-alpha therapy may be useful in assessing the risk of patients developing autoimmune disease.