A new glomerular antigen in passive Heymann's nephritis

Abstract

Within 20 min after i.v. injection or unilateral renal perfusion of rabbit anti-rat proximal tubular brush border antigens (RARFAXIA) into rats, fluorescence microscopy (FM) demonstrated rabbit IgG (RIgG) in a linear fashion along the endothelial region of the glomerular capillary walls. This finding was confirmed by immuno-electron microscopy (IEM) which revealed the presence of reaction product on the plasma membranes of the endothelial cells. Between 8 h and 26 days following i.v. injection of RARFXIA, granular subepithelial deposits of RIgG were demonstrated by FM and IEM, and the endothelial localization seen at earlier time periods was no longer present. In the later time periods after loss of RIgG from the endothelial region, a second injection of RARFXIA did not result in binding of IgG to this site suggesting loss of the antigen or impairment in antigen-antibody binding affinity. Evidence for depletion of endothelial binding antibody from the circulation was derived from passive transfer experiments, in which sera were harvested from rats either 20 min or 48 h following i.v. injection of RARFXIA-I125. When equivalent doses of these sera were perfused into kidneys of normal rats, minimal glomerular binding was demonstrated with sera obtained at 20 min, but no binding to the capillary wall was observed with sera obtained at 48 h. These observations demonstrate that immediately after the induction of passive Heymann's nephritis (PHN) with the complex polyclonal antibody to FXIA, an antigen-antibody reaction occurs along the endothelial region of the glomerular capillary and that later in the course of the disease in vivo, antibody binding to this site is abrogated. The relationship of this early event to the ultimate development of subepithelial deposits is unknown. This reaction may be a source of immune complexes which migrate through the glomerular basement membrane (GBM) or the early binding of the antibody to an endothelial antigen(s) may result in altered permeability of the glomerular capillary allowing other antibodies to find their putative antigen(s).