Heparan sulfate staining of the glomerular basement membrane in relation to circulating anti-RNA and anti-heparan sulfate reactivity: A longitudinal study in NZB/W F1 mice

Reactivity of serum antibodies with heparan sulfate (HS) has been associated with human and murine lupus nephritis, although the aetiological significance of this association is not clear. Recent work from our laboratories showed that binding of these antibodies to HS could be mediated by histone containing immune complexes. In human lupus nephritis we found a strong decrease in HS staining in the glomerular basement membrane (GBM). The aim of this study was to elucidate the correlation in experimental systemic lupus erythematosus (SLE) between albuminuria, staining of HS in the GEM and anti-DNA and anti-HS reactivity in plasma. We therefore studied NZB/W F1 mice during different stages of glomerular disease and compared them with age matched control NZB/W F1 mice without albuminuria. Anti-DNA and anti-HS reactivity were measured in longitudinally collected plasma samples and correlated with the onset of albuminuria, staining of HS in the glomerular basement HS staining was of mice with prolonged proteinuria in comparison with age matched control mice (P=0.0013). This decreased HS staining was correlated with increased Ig deposition in the capillary loops (tau=-0.42,