Possible pathogenic role of cationic anti-DNA autoantibodies in the development of nephritis in patients with systemic lupus erythematosus.

Extensive studies in murine models of lupus nephritis have shown that cationic anti-DNA autoantibodies have nephritogenic potential. We have investigated whether cationic anti-DNA antibodies of IgG class are also produced in vivo in patients with active lupus nephritis. Antibodies against DNA in the sera from patients with SLE were purified by affinity chromatography on DNA-cellulose, followed by nonequilibrium pH gradient electrophoresis and SDS-PAGE. The highly cationic anti-DNA antibodies of IgG class were prominent in the nonequilibrium pH gradient electrophoresis-immunoblots of the antibodies from the patients with active lupus nephritis. Decreased proteinuria after successful treatment with prednisolone was associated with disappearance of the cationic anti-DNA antibodies in the circulation. The cationic anti-DNA antibodies did bind to heparan sulfate, which is a major glycosaminoglycan in glomerular basement membrane, much better than did neutral anti-DNA antibodies. The results suggest that the cationic anti-DNA autoantibodies may play a certain role in the development of lupus nephritis. Our study demonstrates the strong association between the presence of cationic anti-DNA antibody and the development of lupus nephritis in humans.