Increased urinary excretion of C5b-9 distinguishes passive Heymann nephritis in the rat.
Increased urinary excretion of C5b-9 distinguishes passive Heymann nephritis from other forms of experimental glomerulonephritis in the rat. In the passive Heymann nephritis (PHN) model of membranous nephropathy (MN) subepithelial deposits form from anti-Fx1A antibody reacting with antigen expressed on the glomerular epithelial cell membrane followed by membrane patching and shedding of immune complexes. Immune complex deposits are accompanied by deposits of C5b-9 which is required for the mediation of proteinuria. We tested the hypothesis that C5b-9 assembly on the epithelial cell membrane might result in C5b-9 excretion in the urine, which would distinguish this autoimmune mechanism of MN from other processes that result in subepithelial immune complex deposits. Using monoclonal antibodies developed to rat C6 and a rat C5b-9 neoantigen, in a sensitive ELISA assay, elevated urinary excretion of rat C5b-9 was documented in PHN associated with on-going glomerular immune deposit formation. No urinary C5b-9 was detectable in MN induced by an exogenous antigen (cationized IgG) despite equivalent glomerular C5b-9 deposits, or in models of nephrotoxic nephritis, subendothelial immune complex nephritis, anti-mesangial cell membrane antibody-induced nephritis or two non-immune nephropathies. Infusion of preformed C5b-9 in proteinuric animals excluded glomerular filtration of C5b-9 as a contributing mechanism to urinary C5b-9 excretion. We conclude that in the rat, increased urinary excretion of C5b-9 is a marker of MN induced by antibody to a glomerular epithelial cell antigen. Urine C5b-9 excretion reflects active glomerular immune deposit formation and distinguishes MN induced by this mechanism from other forms of MN as well as from other glomerular diseases with equivalent glomerular C5b-9 deposits.
Schulze
M
M
Department of Medicine, University of Washington, Seattle.
Baker
P J
PJ
Perkinson
D T
DT
Johnson
R J
RJ
Ochi
R F
RF
Stahl
R A
RA
Couser
W G
WG
D000818:Animals; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex / Q000276:immunology; D015938:Complement Membrane Attack Complex; D003165:Complement System Proteins / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D005921:Glomerulonephritis / Q000276:immunology / Q000652:urine*; D007678:Kidney Glomerulus / Q000276:immunology; D008297:Male; D051381:Rats
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D015938:Complement Membrane Attack Complex; D003165:Complement System Proteins