Autoimmune Renal Injury in C3- and C4-Deficient Mice: A Histological and Functional Study

Abstract

Background: Complement deficiency predisposes to autoimmune renal disease. Since complement deficient mice are increasingly used to study the immunopathogenesis of renal disease we have determined whether mice deficient in C3 or C4 are susceptible to spontaneous immune-mediated renal injury. Methods: C3-deficient, C4-deficient and complement-sufficient, wild-type mice were maintained in standard conditions for 1 year at which stage renal function, renal histology, circulating antibody and autoantibody levels were assessed. Results: No significant decline in renal function was demonstrated in the complement-deficient mice. However, there was histological evidence of glomerular injury in both the C3- and C4-deficient mice, but of insufficient severity to alter function. Serum IgG2a concentration was significantly lower in C3- and C4-deficient mice. In contrast C3-deficient mice had higher concentrations of serum IgG2b. There was a tendency for mice from all groups, including the complement-sufficient mice, to develop autoantibodies. C4-deficient mice had higher titres of anti-dsDNA IgG but otherwise deficient mice had similar autoantibody titres to controls. Conclusion: We conclude that C4-deficient mice demonstrate a small increase in autoantibody production at 1 year of age compared to C3-deficient and wild-type mice. Furthermore, although complement-deficient mice exhibit glomerular changes, they are of minor functional significance, and are unlikely to affect the study of experimentally induced renal disease in these mice.

Clinical characteristics of IgA nephropathy associated with low complement 4 levels

“…This association has also been demonstrated in previous studies in animal models. 34,35 The neutrophil recruitment in kidney and proteinuria were alleviated in the C4-deficient mice with either anti-glomerular basement membrane (GBM)-mediated nephritis 36 or acute nephrotoxic serum nephritis. 37 Though C3 is an essential factor in complement system, the analyses of the patients with low C3 levels and the subgroup analysis showed that C3 levels were not significantly associated with renal injury at baseline.…”