Antibody-mediated injury to proximal tubules in Heymann nephritis

Abstract

To evaluate the hypothesis that antibody-mediated damage to proximal tubules (PT) could be a feature of Heymann nephritis (HN), we studied the kidneys of rats in different stages of the disease by light, immunoflourescence (IF), transmission, and scanning electron microscopy. The observations of morphology were correlated with titers of circulating antibodies directed against the brush border (BB) and with proteinuria. Antibody titers reached a maximum 5 to 7 weeks after immunization with Fx1A, coincident with the onset of proteinuria. IgG and C3 were deposited along the BB of PT in all animals within the first week of proteinuria. BB antibodies were present in the urine of those rats. As antibody titers declined, a decrease in the extent of in vivo IgG deposition along the BB was also noted. The results of indirect IF tests, by using BB antibodies on kidneys of rats with HN of 3 to 4 months' duration, suggested extensive loss of the BB antigen(s) from the PT. Numerous granular deposits of IgG were present along the basement membrane of PT at that time. Study of kidney histology revealed that deposition of IgG and C3 along the BB of PT was associated with extensive loss of microvilli, as well as degeneration and proliferation of PT cells. Subepithelial electron-dense deposits were present along the basement membrane of PT. In rats with HN of more than 4 months' duration, with little or no circulating BB antibodies and persistent proteinuria, IgG and C3 were found in minimal amounts along BB. Examination by light and electron microscopy provided evidence of partial recovery of PT lesions in those kidneys. Rats with similar proteinuria resulting from chronic serum sickness did not have similar abnormalities of PT. These observations are consistent with the interpretation that, in rats with HN, BB antibodies induce cytotoxic injury to PT.