Cytotoxic islet cell autoantibodies in newly diagnosed insulin-dependent diabetes mellitus: lack of correlation to age, residual beta cell function, HLA antigens and Coxsackie B virus antibodies.

In a cross-sectional study comprising of 56 patients with newly diagnosed insulin-dependent diabetes mellitus (IDDM) serum was examined for the presence of complement-dependent antibody mediated cytotoxicity (C'AMC) by an improved assay measuring the release of 51Cr from freshly isolated normal rat islet cells prelabeled with the isotope. In the presence of complement, 35 (63%) IDDM sera specifically mediated cytotoxicity against islet cells. The degree of cell specificity was tested using prelabeled exocrine cells, but this cell type did not reveal any differences between the lytic effects of IDDM and control serum. At the time of clinical onset of IDDM the age of the patients, fasting and stimulated C-peptide levels, insulin requirement, HLA antigens, antibodies to Coxsackie B1-6 viruses, diabetes heredity, and, surprisingly, islet cell surface antibodies (ICSA) were not associated with C'AMC. It is concluded that the mere presence of C'AMC against rat islet cells at the time of diagnosis of IDDM is not indicative of a low residual B cell function and HLA-linked susceptibility to diabetes does not necessarily include enhancement of humoral anti-islet cell autoimmunity. More elaborate methods for quantitative detection of C'AMC and ICSA (e.g. in terms of titres) together with autoantibody subclass determination are needed to reveal possible associations between C'AMC and the clinical characteristics of IDDM.