THE KINETICS OF THE PATHOGENIC PRONASE-DIGESTED RENAL PROXIMAL TUBULAR ANTIGEN AND ANTIBODY IN RAT ACTIVE HEYMANN NEPHRITIS

We investigated the pathogenesis of active Heymann nephritis in the ra t by conducing immunofluorescent and immunoblotting studies of the pat hogenic antigen and the autoantibody, and by detecting this antigen-bo und IgGs. Rat IgG was detected along the glomerular basement membrane (GEM) and significant proteinuria was observed 6 weeks after the injec tion of rat pronase-digested tubular brush border antigen. Circulating antibody which bound only to the brush border of proximal tubules of normal rat, appeared 2 weeks after antigen injection. fluted antibody from nephritic kidney 6 weeks after immunization bound exclusively to the brush border of the proximal tubules of normal rat kidney. Monoclo nal antibody against the nephritogenic 0.3 M antigen, which bound excl usively to the brush border in the normal rat, bound to the GEM in a f ine granular fashion, as well as to the brush border from nephritic ra ts, indicating the deposition of nephritogenic 0.3 M antigen in the GE M of nephritic rats. On immunoblotting, both the circulating antibody and eluted antibody obtained from the nephritic kidney 6 weeks after i mmunization recognized the 0.3 M antigen. This antigen-bound IgG appea red in circulation at 2 weeks, becoming smaller in size at 4 weeks and disappearing 12 weeks after immunization. Thus, it is suggested that active Heymann nephritis in rats was induced by deposition of the circ ulating 0.3 M antigen-bound IgG complexes in the subepithelial space o f GBM.