The Kinetics of the Pathogenic Pronase-Digested Renal Proximal Tubular Antigen and Antibody in Rat Active Heymann Nephritis

Abstract

We investigated the pathogenesis of active Heymann nephritis in the rat by conducting immunofluorescent and immunoblotting studies of the pathogenic antigen and the autoantibody, and by detecting this antigen-bound IgGs. Rat IgG was detected along the glomerular basement membrane (GBM) and significant proteinuria was observed 6 weeks after the injection 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. Eluted antibody from nephritic kidney 6 weeks after immunization bound exclusively to the brush border of the proximal tubules of normal rat kidney. Monoclonal antibody against the nephritogenic 0.3 M antigen, which bound exclusively to the brush border in the normal rat, bound to the GBM in a fine granular fashion, as well as to the brush border from nephritic rats, indicating the deposition of nephritogenic 0.3 M antigen in the GBM of nephritic rats. On immunoblotting, both the circulating antibody and eluted antibody obtained from the nephritic kidney 6 weeks after immunization recognized the 0.3 M antigen. This antigen-bound IgG appeared 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 circulating 0.3 M antigen-bound IgG complexes in the subepithelial space of GBM.