The interaction of anti-glomerular basement membrane antibody deposition with immune elimination of bovine serum albumin in the rabbit

Abstract

We studied the interaction of two different forms of immune glomerular damage occurring simultaneously: anti-glomerular basement membrane (GBM) antibody fixation and immune elimination of bovine serum albumin (BSA). 125I-radiolabelled BSA anti-BSA immune complexes, formed in response to a single small intravenous dose (150 mg/kg) of 125I BSA, did not cause proteinuria in control animals within 15 days, despite evidence of immune elimination of the antigen. Similarly, a small dose of nephrotoxic globulin (NTG)(3.0 mg/kg) did not cause immediate proteinuria in controls. Test animals received the BSA injection followed by the NTG injection 5, 7 or 9 days later. In this way, antibody fixed to glomerular basement membrane antigens at various times after BSA anti-BSA complexes first appeared in the circulation. Animals were killed on day 15. Fifteen of the eighteen test animals developed moderate to severe clinical nephritis. The onset of the nephritis coincided with BSA elimination irrespective of when the NTG was given. Greatly increased amounts of nonlinear immunofluorescent deposits were demonstrated in the glomeruli of test animals. We concluded that there was a marked synergistic effect between two forms of immune glomerular damage (i.e. that mediated by anti-GBM antibody and immune complexes), which appeared to be due to the increased deposition of complex material in the presence of active fixation of anti-GBM antibody. The relevance of this finding to human glomerulonephritis is discussed.