COMPLEMENT-FIXING ISLET-CELL ANTIBODIES IN TYPE-1 DIABETES CAN TRIGGER THE ASSEMBLY OF THE TERMINAL COMPLEMENT COMPLEX ON HUMAN ISLET CELLSAND ARE POTENTIALLY CYTOTOXIC

Forty-one sera of patients with IDDM (insulin-dependent diabetes melli tus) containing complement fixing islet cell antibodies were analyzed for their ability to activate TCC (terminal complement complex). Eight een sera were found to promote deposition of TCC on human islets of pa ncreatic cryostat sections with a nonhomogeneous pattern of distributi on corresponding to that of insulin. Activation of TCC by IDDM serum a nd binding of this complex to islet cells was confirmed using purified islets. Flow cytometric analysis of islet cell treated with a TCC+ ID DM serum showed IgG binding to the cell surface. The same serum had a cytotoxic effect on islet cells in the presence of human C. These resu lts obtained with a homologous system of C activation by IDDM sera sug gest that TCC may contribute, at least in part, to the pancreatic beta cell damage. (C) 1996 Academic Press, Inc.