Glomerular deposition and urinary excretion of complement factor H in idiopathic membranous nephropathy.
OBJECTIVE
The complement system plays an important role in the pathogenesis of membranous nephropathy (MN). In order to elucidate the regulatory mechanism of complement activation, we demonstrated glomerular deposition and urinary excretion of complement factor H, which controls the alternative pathway and the amplification loop at the C3 step, in patients with idiopathic MN.


METHODS
Renal biopsy specimens from 20 patients with idiopathic MN were studied immunohistochemically using monoclonal antibodies against complement components including factor H. SDS-PAGE and Western blotting analysis of urine samples were performed, and the urinary excretion of factor H and C5b-9 were measured by quantitative sandwich ELISA.


RESULTS
Intense glomerular deposition of factor H was observed with C3b.C3c and C5b-9 at an early stage of the disease. Factor H was detected in Western blots of urine samples, but factor H-like protein 1 (FHL-1) was not. The mean level of urinary factor H was elevated (86.30 +/- 21.93 U/mg urinary creatinine) in comparison to that of normal controls (4.76 +/- 1.03 U/mg urinary creatinine). Urinary factor H level exhibited no correlation with clinical parameters; however, a negative correlation was found between urinary C5b-9/factor H and creatinine clearance (r = 0.662, p < 0.01).


CONCLUSIONS
The source of glomerular and urinary factor H is supposedly a 150-kD protein. There was no evidence to suggest that FHL-1 is synthesized at the site of inflammation. The urinary C5b-9 to urinary factor H ratio is indicative of the degree of ongoing complement activation in the glomeruli and complement-mediated renal injury. These findings suggest that factor H contributes to the control mechanism of in situ complement activation and prevents renal damage in idiopathic MN.
Endo
Morito
M
Division of Nephrology, Internal Medicine II, Nihon University School of Medicine, Tokyo, Japan. mendo@chojuken.net
Fuke
Yoshinobu
Y
Tamano
Mariko
M
Hidaka
Mutsuko
M
Ohsawa
Isao
I
Fujita
Takayuki
T
Ohi
Hiroyuki
H
D017398:Alternative Splicing; D001706:Biopsy; D001798:Blood Proteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics; D015153:Blotting, Western; D003179:Complement C3b / Q000032:analysis; D015932:Complement C3c / Q000032:analysis; D017242:Complement Factor H / Q000032:analysis / Q000737:chemistry / Q000502:physiology / Q000652:urine*; D015938:Complement Membrane Attack Complex / Q000032:analysis / Q000652:urine; D003170:Complement Pathway, Alternative; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000378:metabolism / Q000652:urine*; D006801:Humans; D007678:Kidney Glomerulus / Q000737:chemistry* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight
D001798:Blood Proteins; C493495:CFH protein, human; D015938:Complement Membrane Attack Complex; C100631:factor H-related protein 1; D003179:Complement C3b; D015932:Complement C3c; D017242:Complement Factor H