Chronic serum sickness glomerulonephritis: modification of the immune response influences the rate of removal of mesangial electron-dense deposits

Abstract

We have used a chronic serum sickness model of glomerulonephritis to investigate whether gross interference with the immune system can influence the rate of removal of antigen and established electron-dense deposits from the glomerulus. Radio-labelled cationized bovine serum albumin (BSA) was used as antigen. During the 2 weeks after the cessation of injections, the rate of removal of antigen from isolated glomeruli and from renal cortex, liver, spleen, and lung was measured. The rate of removal of mesangial and subepithelial deposits was assessed by point-counting. Urinary excretion of free and protein-bound isotope was also measured. Having quantified the rate of removal of antigen and deposits from the glomerulus, we attempted to influence the rate of removal by interfering with the immune response in the course of recovery. Contrary to our expectations, stimulation of the immune system with antigen in Freund's complete adjuvant, 4 days after the last injection of antigen, inhibited the removal of antigen and mesangial electron-dense deposits. Prednisolone had no detectable effect, but large doses of a non-nephritogenic form of the antigen (native BSA) enhanced removal. Removal of antigen and mesangial deposits was inversely correlated with the levels of circulating anti-BSA antibody, suggesting that specific antibody, circulating through the mesangium, inhibits the removal of antigen which is already trapped at that site. None of the forms of intervention applied during recovery produced a detectable change in the rate of removal of subepithelial deposits.