The relationship between hyperglycaemia and renal immune complex deposition in mice with inherited diabetes.

Kidney lesions were studied by light microscopy and immunofluorescence in diabetic (db/db) and obese (ob/ob) mutant mice. The db/db mutation was studied both on the C57Bl/KsJ genetic background (where it produces severe hyperglycaemia) and on the C57Bl/6J background (where hyperglycaemia is only mild). In all cases, more IgG, IgM and C3 were deposited in the renal glomeruli of mutant mice than in the glomeruli of normal (+/?) mice of equivalent age. First signs of immunoglobulin deposition occurred at a slightly younger age than first signs of C3 deposition or histological change (mainly mesangial thickening). Insulin deposits were occasionally seen in the glomeruli of older mutant mice and immunoglobulin eluted from diabetic mouse kidneys had anti-insulin activity. Increased anti-DNA activity was present in the serum of older mutants. In those mutants with severe hyperglycaemia, the macula densa and distal convoluted tubules also contained immunoglobulin deposits, probably derived from the glomerular mesangium. Urine from diabetic mice contained high molecular weight material reacting with antisera to Fab or kappa but not the Fc portion of immunoglobulin. We conclude that diabetic mice have immune complexes in the kidney containing antibodies against insulin and possibly other antigens. We find no evidence that hyperglycaemia itself is the direct cause of glomerular immune complex deposition, although there may be a link between hyperglycaemia and tubular dysfunction.