Factors affecting severity of injury during nephrotoxic nephritis in rabbits

All 22 rabbits injected with sheep globulin containing high titres of antibodies to rabbit glomerular basement membrane (GBM)--nephrotoxic globulin (NTG)--developed antibodies to sheep IgG. Despite this only 15 rabbits developed obvious autologous phase injury. Eleven days after injection of NTG titres of autologous antibody to sheep IgG were similar in rabbits with and without definite autologous phase injury but were detected earlier and rose significantly more rapidly in those with autologous phase injury. In experiments on heterologous phase injury after intravenous injection of NTG, binding of defined amounts of nephrotoxic antibodies (NTAb) to the GBM after bolus injection caused significantly more injury, assessed by proteinuria, than binding of similar amounts of NTAb after infusion of NTG over 3 h (P less than 0.02 Student's paired t-test). In in vitro experiments, aliquots of homogenized rabbit kidney taken 2 days after injection of NTG bound appreciable amounts of rabbit anti-sheep Ig whereas homogenates of kidneys taken 20 days after NTG showed no such binding. These results show that the rate of deposition of NTAb in kidney influences the severity of injury in heterologous and autologous phases of NTN and that antigenic sites or heterologous IgG fixed to the GBM become saturated during the autologous phase of injury.