IgG subclasses of islet cell surface antibodies and their cytotoxic activity against pancreatic islet cells

IgG subclasses of islet cell surface antibodies (ICSA) and their cytotoxic activities against pancreatic islet cells in the presence of complements were simultaneously investigated in ICSA-positive patients with insulin-dependent diabetes mellitus (n = 15). ICSA (IgG class) and ICSA-IgG subclasses were determined by flow cytometry using a fluorescence-activated cell sorter (FACS). Complement-dependent antibody-mediated cytotoxicity (CAMC) was measured by release of 51Cr from target cells. For these assays, rat insulinoma (RINr) cells were used as antigenic or target cells. Sera from 11 out of 15 patients who were positive for ICSA possessed at least one positive ICSA-IgG subclass, though these sera did not always exert positive CAMC activities. When the relationship between ICSA-IgG subclasses and CAMC was tested by chi-square analysis, a significant relationship (P less than 0.01) was observed between ICSA-IgG3 and CAMC. In sera from the other four patients, not any positive ICSA-IgG subclass or CAMC activity was found. The data suggest that (1) ICSA (IgG class) found in diabetics are not always cytotoxic to pancreatic islet cells, (2) the IgG subclass of ICSA varies with the patients, and (3) ICSA-IgG3 have a significantly higher association with CAMC to pancreatic islet cells. Thus, ICSA (IgG class) might not always be responsible for the impairment of pancreatic islet cells, at least in part, because of the heterogenous ICSA-IgG subclass.