Cytotoxic antibodies to cloned rat islet cells in serum of patients with diabetes mellitus.

We have found complement-dependent cytotoxic antibodies in the serum of 8 of 24 patients with insulin-dependent diabetes mellitus using a 51Cr cytotoxicity assay with monolayers of cloned rat islet cells (clones RINm 5F and RINm 14B). In contrast, complement-dependent cytotoxicity with 51Cr release greater than 24% was found with sera from 34 controls or from 5 patients with polyglandular failure without diabetes, and was present in only 1 serum our of 12 from patients with insulin-independent diabetes mellitus. The prevalence of antibodies appears to decrease with duration of insulin-dependent diabetes, and in one patient studied, cytotoxic antibodies were present at the time of diagnosis of diabetes. Cytotoxicity is independent of insulin synthesis, as evidenced by the linear correlation of cytotoxicity of sera for the insulin-producing clone RINm 5F and the somatostatin-producing clone RINm 14B. The present study identifies nonspecies-specific cytotoxic antibodies in the serum of patients with diabetes mellitus, and the assay used should facilitate studies of humoral immunity in the pathogenesis of diabetes mellitus.