High serum levels of soluble CD8 in insulin-dependent diabetes.

In type 1 (insulin-dependent) diabetes mellitus (IDDM) CD8+ T cells represent the majority of lymphocytes which infiltrate the pancreatic islets during beta cell destruction. Soluble CD8 antigen (sCD8) has been shown to correlate with CD8 cell subset activation. In this study we measured by ELISA sCD8 levels in sera from: 33 newly diagnosed IDDM patients; 29 type 1 diabetics with duration of disease more than 1 year; 37 healthy siblings of IDDM patients; 19 healthy controls. Sera from both groups of IDDM patients and from healthy siblings exhibited soluble CD8 mean levels significantly higher than controls (P = 0.0001, P < 0.003, P < 0.03 respectively). Soluble CD8 levels above the normal range (mean +/- 2 s.d. of controls) were found in a percentage of newly diagnosed subjects (54.5%) significantly higher than in subjects with a long-standing duration of disease (6.9%, P < 0.0005) and healthy siblings (16.2%, P < 0.002). Our results suggest that the raised levels of soluble CD8 near to diabetes onset may indicate the activation of CD8+ T cells probably responsible for the autoimmune beta cell destruction.

Interferon-alpha therapy may induce insulin autoantibody development in patients with chronic viral hepatitis.

Development of type 1 insulin-dependent diabetes mellitus has been recently reported in patients who underwent interferon-alpha (IFN-alpha) therapy because of chronic viral hepatitis. Furthermore IFN-alpha seems to be involved in the immunological events that lead to beta-cell destruction and development of type 1 diabetes. To evaluate whether IFN-alpha treatment could elicit an autoimmune response against beta-cell antigens, we determined the occurrence of islet cell antibodies and insulin autoantibodies in the sera of 60 patients with HCV- or HBV-related chronic hepatitis who had been treated with IFN-alpha for 6 or 12 months. The presence of antibodies against thyroglobulin, thyroid microsomal antigen, gastric parietal cells, and non-organ-specific antigens was also investigated. Insulin autoantibody positivity was observed in 2/60 (3.3%), 8/60 (13.3%), and 4/30 (13.3%) patients, before IFN-alpha treatment, and after 6 months and 12 months of therapy, respectively. None of the studied patients developed islet cell antibodies or type 1 diabetes. Before IFN-alpha therapy four patients showed thyroid autoantibodies and four others developed antibodies against thyroglobulin and/or thyroid microsomal antigen during the treatment. Coexistence of insulin autoantibodies and thyroid autoantibodies was observed in only two patients. Our results showed that IFN-alpha therapy in patients with chronic viral hepatitis is capable of inducing development of autoantibodies against insulin. This event seems to be not related to other autoimmune disorders.