DECREASE OF HEPARAN-SULFATE STAINING IN THE GLOMERULAR-BASEMENT-MEMBRANE IN MURINE LUPUS NEPHRITIS

Recently we found in biopsies of human lupus nephritis a nearly comple te loss of heparan sulfate (HS) staining in the glomerular basement me mbrane (GBM), To clarify the relationship between NS staining and albu minuria in lupus nephritis, we studied MRL/lpr mice with short (< 7 da ys) or prolonged duration of albuminuria (14-21 days) and compared the se with mice of different ages without albuminuria. Kidney sections we re stained for mouse immunoglobulin (Ig), HS, heparan sulfate proteogl ycan (HSPG)-core protein and laminin in immunofluorescence. In mice wi th prolonged albuminuria HS staining in the glomerular capillary loops had almost completely disappeared, whereas staining was unaltered in non-albuminuric mice (P = 0.001). In mice with short duration of album inuria, there was a tendency toward a decrease of NS staining (P = 0.0 6). The expression of HSPG-core protein and other extra cellular matri x (ECM) components was unaltered in all groups. HS staining correlated inversely with albuminuria (r(s) = -0.55; P < 0.001) and with stainin g of Ig deposits in the capillary loops (r(s) = -0.74; P < 0.001). Des pite the nearly complete loss of HS staining in the GBM in mice with p rolonged albuminuria, there was no change in glomerular HS content as assessed by agarose electrophoresis and HS inhibition ELISA. We conclu de that the development of albuminuria in MRL/lpr mice is accompanied by a loss of HS staining in the GBM, probably due to the masking of NS by deposits of Ig. In vitro studies revealed that autoantibodies comp lexed to nucleosomal antigens can inhibit the binding of the anti-HS m onoclonal antibody to HS. Whether this also occurs in vivo remains to be determined.