Urinary excretion of C5b-9 reflects disease activity in passive Heymann nephritis.
Passive Heymann nephritis (PHN) is a model of membranous nephropathy in rats in which glomerular injury is mediated by the terminal C5b-9 membrane attack complex of complement. This model has been shown to be associated with markedly elevated urinary excretion of C5b-9, compared to other experimental models of glomerulonephritis To determine if urinary C5b-9 excretion could serve as an index of disease activity by correlating with the formation and quantity of glomerular subepithelial immune deposits in PHN, we measured urinary excretion of C5b-9 in PHN under several experimental conditions. In the heterologous phase a direct correlation was demonstrated between levels of urinary C5b-9 excretion and the amount of anti-Fx1A IgG deposited in glomeruli (r = 0.85). In the autologous phase, C5b-9 excretion correlated with the amount of deposit forming antibody present in the serum and resolved when antibody disappeared, despite persistence of glomerular deposits of antigen, antibody, C5b-9 and heavy proteinuria. Glomerular C3 deposits paralleled urinary C5b-9 excretion. Re-initiation of active deposit formation by a second injection of anti-Fx1A produced new C3 deposits and a marked rise in C5b-9 excretion. Finally, complete abrogation of deposit formation by transplanting PHN kidneys into normal recipients also halted C5b-9 excretion. Our findings demonstrate that urinary excretion of C5b-9 is a sensitive index of on-going immunologic disease activity in the PHN model of membranous nephropathy.
Pruchno
C J
CJ
Department of Medicine, University of Washington, Seattle.
Burns
M W
MW
Schulze
M
M
Johnson
R J
RJ
Baker
P J
PJ
Couser
W G
WG
D000818:Animals; D000906:Antibodies / Q000378:metabolism; D015415:Biomarkers / Q000652:urine; D015938:Complement Membrane Attack Complex / Q000652:urine*; D005455:Fluorescent Antibody Technique; D005921:Glomerulonephritis / Q000276:immunology* / Q000652:urine; D007074:Immunoglobulin G / Q000276:immunology; D007678:Kidney Glomerulus / Q000276:immunology*; D016030:Kidney Transplantation; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D012756:Sheep
D000906:Antibodies; D015415:Biomarkers; D015938:Complement Membrane Attack Complex; D007074:Immunoglobulin G