Polyreactive Autoantibodies Are Nephritogenic in Murine Lupus Nephritis

To characterize the antibodies that form glomerular immune deposits in lupus nephritis, immunoglobulin (Ig) was eluted from the perfused kidney cortices of female MLR-lpr/lpr mice with early nephritis. The eluted Ig was predominantly IgG with antibody activity against DNA, multiple polynucleotides, SmRNP, gp70, and levan that was greater than the serum antibody activity of age- and sex-matched mice. Of particular interest, both kidney eluate and serum anti-DNA antibodies were observed to cross-react with multiple polynucleotides; however, only the kidney eluate Ig cross-reacted with phospholipids and RNA. Furthermore, the anti-DNA antibodies in the kidney eluate also cross-reacted with SmRNP and gp70; these ligand-binding properties were shared by the Ig in the kidney eluate that did not bind to DNA; and both kidney eluate fractions shared Id-H130 activity (a high frequency MRL-1pr/1pr idiotype). In contrast, the spectrotypes of Ig in the kidney eluate were found to be similar to serum, and they were observed to be between isoelectric points 6.5 to 7.8. Both the anti-DNA antibodies and the Ig that did not bind to DNA had similar isoelectric points throughout this entire range. These findings indicate that polyreactivity is a distinguishing feature of nephritogenic autoantibodies. They also raise the possibility that these ligand-binding properties influence the capacity of autoantibodies to form immune deposits. This influence could occur because polyreactive antibodies cross-react with antigenic determinants within the normal glomerular capillary wall. Alternatively, polyreactive antibodies may more readily form circulating immune complexes that are, in turn, passively trapped within the glomerulus.