Enhancement of hydroxyl radical DNA cleavage by serum anti-dsDNA antibodies in SLE

Autoantibodies reactive with double-stranded (ds) DNA are a hallmark of systemic lupus erythematosus (SLE), but it is not fully elucidated how these antibodies contribute to the various pathological changes observed in lupus patients. In a previous study, we have found a significant enhancement effect of two murine monoclonal anti-dsDNA antibodies on DNA cleavage by the hydroxyl radical. We have extended this study and have found that purified polyclonal anti-dsDNA antibodies from sera of lupus patients and an MRL/lpr mouse, but not anti-ssDNA antibodies, also enhanced radical cleavage of DNA. The cleavage was inhibited by EDTA, DMSO and thiourea. The antibody preparations per se did not cleave DNA. These results suggest that such an enhancement effect on DNA cleavage is a feature of a significant part of anti-dsDNA antibody population and a possible clue in understanding the roles of anti-dsDNA antibodies in the pathophysiology of SLE under certain circumstances.