Chronic nephritis induced by antibodies reacting with glomerular-bound immune complexes

The pathogenesis of chronic membranous glomerulonephritis induced in rats by passive immunization with heterologous antibodies to rat renal tubular epithelial (RTE) antigens was investigated. This model is designated as "passive Heymann nephritis" (PHN) in order to contrast it with classical Heymann nephritis induced by active immunization with homologous RTE in adjuvant. A single i.v. injection of heterologous (rabbit) antibody to RTE evoked chronic proteinuria after a latent period of one to three days. The onset of proteinuria was accompanied by the granular deposition of rabbit IgG and rat beta1C globulin along the glomerular capillary wall. Renal isografts developed PHN only when transplanted within the first three days following injection of the heterologous anti-RTE antibodies. The data suggest that the heterologous antibodies form immune complexes with RTE antigens preexisting in the circulation, and these complexes subsequently deposit in the glomerular capillary walls. Chronic proteinuria is then perpetuated by a host reaction to the foreign protein in the deposits (i.e., rabbit IgG), in a fashion analogous to that seen in the autologus phase of nephrotoxic serum nephritis. These studies indicate that continued glomerular deposition of preformed circulating immune complexes may not always be a requisite for the perpetuation of glomerular injury in immune complex disease.