Brief DeNnitive Report CLEARANCE OF CIRCULATING DNA-ANTI-DNA IMMUNE COMPLEXES IN MICE* BY WOODRUFF EMLEN AND MART MANNIK

I m m u n e complexes composed of DNA and antibodies to DNA contribute to tissue injury in systemic lupus erythematosus (SLE) (1, 2). High titers of antibodies to both single-stranded D N A (ssDNA) and double-stranded D N A (dsDNA) are associated with the disease (2, 3), and antibodies to DNA have been eluted from the kidneys of SLE patients (4, 5). Direct demonstrat ion of circulating DNA-an t i -DNA immune complexes has been reported (6, 7), but not confirmed (8). Whereas the fate of circulating immun e complexes such as HSA-an t i -HSA has been well characterized (9), the behavior of immune complexes containing D N A has not been studied. D N A is cleared from the circulation extremely rapidly, faster than large-latticed complexes (10). Furthermore, in vitro D N A binds to glomerular and skin basement membranes (11). These unique features of DNA might also influence the fate of immune complexes containing DNA as the antigen. In this study, immune complexes were prepared in vitro with ssDNA and antibodies to DNA from a patient with SLE. The clearance and organ localization of these immune complexes was studied in normal mice and compared with the clearance of heat aggregated immunoglobulin (IgG), serving as a model for immune complexes. Our results demonstrate that the clearance of ssDNA-ant i -DNA immune complexes parallels the clearance of DNA alone and is much more rapid than the clearance of aggregated IgG.