Urinary excretion of the C5b-9 membrane attack complex of complement is a marker of immune disease activity in autologous immune complex nephritis.
The urinary excretion of the C5b-9 membrane attack complex of complement correlates with glomerular deposition of antibody in the passive Heymann nephritis (PHN) model of membranous nephropathy (MN). To determine if this parameter can be correlated with antibody deposition in a model of MN induced by an autologous mechanism and thus more analogous to human MN, the relationship of urinary C5b-9 to ongoing glomerular immune complex formation late in autologous immune complex nephritis (AICN) was studied. Based on urinary C5b-9, the animals were divided into two groups at 12 weeks after induction of AICN, those with persistently high urinary C5b-9 excretion and those in whom urinary excretion of C5b-9 returned to undetectable levels. While all rats developed glomerular deposition of rat IgG and significant proteinuria, high C5b-9 excretors had greater proteinuria and prolonged positive staining for glomerular C3. When normal syngeneic kidneys were transplanted into rats (n = 3) from each group, only those with persistent C5b-9 excretion developed subepithelial immune deposits of rat IgG in the transplanted kidney. As in the PHN model of MN, proteinuria was dissociated widely from urinary C5b-9 excretion, glomerular C3 staining, and evidence of circulating antibody. Thus these findings demonstrate that urinary excretion of C5b-9 serves as an index of on-going immunologic disease activity in the AICN model of MN, while proteinuria does not.
Pruchno
C J
CJ
Division of Nephrology, University of Washington, Seattle 98195.
Burns
M M
MM
Schulze
M
M
Johnson
R J
RJ
Baker
P J
PJ
Alpers
C E
CE
Couser
W G
WG
D000818:Animals; D000936:Antigen-Antibody Complex; D015938:Complement Membrane Attack Complex / Q000652:urine*; D005455:Fluorescent Antibody Technique; D007154:Immune System Diseases / Q000503:physiopathology / Q000628:therapy / Q000652:urine*; D007074:Immunoglobulin G / Q000378:metabolism; D007668:Kidney / Q000378:metabolism / Q000648:ultrastructure; D016030:Kidney Transplantation; D009393:Nephritis / Q000503:physiopathology / Q000628:therapy / Q000652:urine*; D051381:Rats
D000936:Antigen-Antibody Complex; D015938:Complement Membrane Attack Complex; D007074:Immunoglobulin G