Cytotoxic Autoantibodies to Beta Cells in the Serum of Patients with Insulin-Dependent Diabetes Mellitus

Abstract We studied serum from 36 patients with insulin-dependent diabetes mellitus (IDDM) for the capacity to lyse beta cells. Immunofluorescence revealed an islet-cell cytoplasmic antibody (ICA) in 20 patients with IDDM and an islet-cell-surface antibody (ICSA) in 23. Neither ICA nor ICSA was found in any of 21 normal controls or 15 patients with non-insulin-dependent diabetes. In the presence of complement, ICSA-positive serum caused significant lysis as measured by release of 51Cr (50.1 ±8.8 per cent) from cultured rat islet cells, but ICSA-negative serum did not (17.7±7.3 per cent) (P<0.001). Proof that ICSA-positive serum was lytic for beta cells was obtained by a double-fluorescence technique that identified lysed cells by their capacity to take up ethidium bromide and beta cells by their staining with fluorescein-conjugated antibody to insulin. These findings suggest that cytotoxic ICSA contributes to the pathogenesis of IDDM, but the mere presence of ICSA does not appear to be sufficient to produ...