Cellular dysfunction induced by penetration of autoantibodies into living cells: Cellular damage and dysfunction mediated by antibodies to dsDNA and ribosomal proteins

Antibodies to dsDNA and ribosomal P proteins are disease specific for systemic lupus erythematosus (SLE) and vary with disease activity. It is thought that antibodies to dsDNA are involved in the pathogenesis of lupus nephritis and clinical data consistent with that hypothesis also exist for anti-ribosomal P antibodies; these two specific antibodies both bind and penetrate cells in culture. In the case of anti-P antibodies, the cellular receptor appears to be a membrane form of the P-o 38 kDa phosphoprotein, which is present on several cell types and appears to mediate the binding and penetration of anti-P antibodies which then localize in the cytoplasm. In the case of anti-dsDNA, numerous cellular receptors exist on various cell types which may account for the three types of behavior demonstrated by antibodies towards dsDNA. These include (a) localization and prolonged residence on the membrane, with prompt cytolysis upon addition of hemolytic complement, (b) penetration and cytoplasmic localization and (c) penetration and nuclear localization. Both anti-P and anti-dsDNA are potent inhibitors of protein synthesis and are likely to mediate cellular dysfunction via this pathway. (C) 1998 Academic Press