Serum C3 and C4 levels and complement-dependent antibody-mediated cytotoxic activity of islet cell surface antibody in type 1 (insulin-dependent) diabetic children.

The role of complement in the pathogenesis of diabetes was studied in 31 Type 1 (insulin-dependent) diabetic children by assaying serum islet cell surface antibody, C3, C4 and serum complement-dependent antibody-mediated cytotoxicity. Nine of 21 islet cell surface antibody-positive children were within 5 months of disease onset and showed significantly lower serum C3 and C4 levels than either 1 year later or the remainder of the islet cell surface antibody-positive children at 6-12 months after disease onset. The overall trend of all islet cell surface antibody-positive diabetic children within 1 year of disease onset was toward increased serum C3 and C4 levels as the disease progressed. Serum C4 concentration and complement-dependent antibody-mediated cytotoxicity which showed an initial negative correlation were uncorrelated 1 year later. Four children who were initially strongly islet cell surface antibody-positive but negative 1 year later also exhibited significantly higher (p less than 0.05) mean serum C4 levels after 1 year. There was a significant decrease in complement-dependent antibody-mediated cytotoxicity when sera from the diabetic children were treated with either ethylene glycol tetra-acetic acid or ethylene diamine tetra-acetic acid. These data strongly suggest that complement-dependent antibody-mediated cytotoxicity induced by the classical complement pathway involving an islet cell surface antibody may play an important role in the pathogenesis of Type 1 diabetes.