SERUM GLOMERULAR BINDING-ACTIVITY IS HIGHLY CORRELATED WITH RENAL-DISEASE IN MRL LPR MICE

The pathogenesis of lupus nephritis is felt to be mediated by anti-DNA antibodies. However, the anti-DNA response and renal disease do not e ntirely correspond. We recently developed a new assay which detects im mune elements based on their ability to bind glomeruli as an alternati ve approach to understanding the pathogenesis of this disorder. The gl omerular binding activity (GBA) defined by this assay consists of immu ne elements containing IgG which interact specifically with renal tiss ue, the binding of which is DNase-inhibitable, but which do not bind t o DNA directly. In the current study we assessed the relationship betw een GBA and renal disease in MRL/lpr mice (both untreated and cyclopho sphamide-treated) and compared it with the anti-DNA assay. Both assays were highly correlated with renal disease in untreated mice in terms of proteinuria. In cyclophosphamide-treated mice, however, only a weak correlation between the anti-DNA assay and proteinuria was apparent. GBA, in contrast, was more strongly correlated with proteinuria in tre ated mice. This correlation improved substantially when the DNase-sens itive component of the GBA was used. GBA appeared related to, but not covariant with, the anti-DNA response. These results demonstrate that GBA is a better correlate of murine lupus nephritis than the anti-DNA assay, and suggest that the immune elements detected by this assay, th e DNase-sensitive component in particular, may be pathogenically impor tant.