Evidence for complement activation in type 1 diabetes

Type 1 diabetes is caused by immune mediated destruction of the beta cells in the pancreatic islets of Lmgerhans. There is evidence that complement activation plays a role in this immune mediated cell death. We have demonstrated a trend towards increased terminal complement complex (TCC, SC5b-9) concentrations in cell culture supernatents of BRIN BDI 1 cells (a rat beta cell line) incubated with 10% v/v serum from patients with newly diagnosed type I diabetes for 24 hours than in supmatents from cells incubated with non-diabetic serum (mean 10,765 (sd 4640) n g / d vs 7939 (sd 1935) ng/mL). Cell viability, assessed by the internal LDH assay, was no different between cells incubated with diabetic and non-diabetic serum. This effect could be abolished by heat treating serum to inactivate complement. TCC levels measured in culture supernatent of pig kidney epithelial cell line (LLC PKI) with 10% diabetic serum were 1007 (sd 95) ng/mL after 24 hours and was 1572 (sd 197) ng/mL with 10 % normal human serum when LLC PKI cells were cultured at the same density as the BDl I cells. This indicates complement activation is cell specific. These results suggest that diabetic serum contains factors that specifically fix complement on beta cells (most likely complement fixing antiislet cell antibodies). Evidence for complement activation in type 1 diabetes 30 Immuno-modulatory mechanisms of E.coli heat labile toxin