ACTIVE HEYMANN NEPHRITIS IN COMPLEMENT COMPONENT C6 DEFICIENT RATS

The mechanisms of renal injury that result in proteinuria in active He ymann nephritis (AHN) remain unclear, though data suggest that in anal ogy of the passive form of the disease the membrane attack complex C5b -9 may be involved. AHN was induced in an inbred strain of PVG/c(-) ra ts that are totally deficient in the C6 component of complement and ar e unable to form the lytic C5b-9 complex, as well as in non-complement deficient PVG/c(+) rats that are immunologic identical to the deficie nt strain. In both groups of animals comparably high titers of anti-Fx 1A autoantibodies were found after three weeks and persisted at 40 wee ks. Proteinuria was also similar in both groups, and was first evident at six weeks. High levels of urinary protein, ranging from 200 mg/24 hr to 500 mg/24 hr, were found after 10 weeks and persisted up to one year. Renal biopsy findings at various times post-immunization were id entical in both groups, including immunofluoresence staining for Ig an d C3 deposits, and also EM findings of subepithelial electron-dense de posits were not different. The injection of heterologous rabbit comple ment, that partially and temporarily restored the CH50 activity in PVG /c(-) rats did not after or hasten the disease. Long-term follow-up sh owed that all rats in both groups continued to have severe proteinuria and that most animals died between 8 to 12 months after disease induc tion, without renal impairment. EM findings in serial biopsies demonst rated that the growth of the subepithelial deposits as measured by sur face area occurred between weeks 4 and 12. A positive correlation (r = 0.94) between the size of the deposits and the level of proteinuria w as found. These studies demonstrate that the membrane attack complex o f complement does not play a major role in AHN. The relationship of th e size of the immune deposits to the level of proteinuria suggests tha t the growth of the immune deposits on itself initiate secondary mecha nisms that damage the permselective characteristics of the glomerular membrane.