Demonstration of apoptosis-associated cleavage products of DNA, complement activation products SC5b-9 and C3d/dg, and immune complexes CIC-C3d, CIC-IgA, and CIC-IgG in the urine of patients with membranous glomerulonephritis.
OBJECTIVE
To investigate the involvement of complement activation and apoptosis in the pathogenesis of membranous glomerulonephritis by determining the concentrations of apoptosis-associated 180 bp nucleosomes and complement activation products SC5b-9 and C3d/dg in the urine of patients with membranous glomerulonephritis.


METHODS
Morning urine was taken from 15 patients with immunohistologically established membranous glomerulonephritis. Apoptosis-associated 180 bp nucleosomes, complement activation products SC5b-9, C3d/dg, and immune complexes CIC-C3d, CIC-IgA, and CIC-IgG were detected in the urine samples by using antigen-specific enzyme-linked immunosorbent assay.


RESULTS
Concentrations of measured parameters were expressed in units of standard deviation, ie, relatively to the average concentrations measured in healthy subjects. We found drastically increased concentrations of apoptosis-associated 180 bp nucleosomes (13.71+/-14.97; p=0.047), complement activation products SC5b-9 (197.07+/-134.88; p=0.003) and C3d/dg (38.70+/-43.35; p=0.048), and immune complexes CIC-C3d (11.01+/-13.39; p=0.74), CIC-IgA (7.93+/-4.38; p=0.001), and CIC-IgG (20.56+/-10.87; p=0.001) in the urine of patients with an active form of membranous glomerulonephritis. All studied molecules were absent, or present in very low concentrations, in healthy subjects and patients with membranous glomerulonephritis in remission. The mean differences between healthy controls and patients with the active disease were statistically significant in all parameters, except CIC-C3d.


CONCLUSIONS
There is an association of complement activation and apoptosis with membranous glomerulonephritis. Correlation analysis suggests that the excretion of apoptosis-associated 180 bp nucleosomes, SC5b-9, C3d/dg, and immune complexes containing IgA and IgG in the urine of patients with active membranous glomerulonephritis does not depend solely on the passive transport together with other proteins, but is probably an independent active process.
Kotnik
Vladimir
V
Institute of Microbiology and Immunology, University of Ljubljana, Korytkova 2, 1000 Ljubljana, Slovenia. vladimir.kotnik@mf.uni-lj.si
Premzl
Ales
A
Skoberne
Mojca
M
Malovrh
Tadej
T
Kveder
Radoslav
R
Kaplan-Pavlovcic
Stasa
S
Kotnik
Antonija
A
Stiblar-Martincic
Draga
D
D000328:Adult; D000368:Aged; D000936:Antigen-Antibody Complex / Q000652:urine*; D017209:Apoptosis; D002455:Cell Division; D003167:Complement Activation; D003179:Complement C3b / Q000652:urine*; D015938:Complement Membrane Attack Complex; D003165:Complement System Proteins / Q000652:urine*; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000652:urine*; D006023:Glycoproteins / Q000652:urine*; D006801:Humans; D007070:Immunoglobulin A / Q000652:urine; D007074:Immunoglobulin G / Q000652:urine; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000652:urine*; D012097:Repressor Proteins / Q000652:urine
D000936:Antigen-Antibody Complex; C498610:CIC protein, human; D015938:Complement Membrane Attack Complex; D006023:Glycoproteins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D010446:Peptide Fragments; D012097:Repressor Proteins; C047610:SC5b-9 protein complex; C045477:complement C3d,g; D003179:Complement C3b; D003165:Complement System Proteins