Extensive complement activation in hereditary porcine membranoproliferative glomerulonephritis type II (porcine dense deposit disease).
Massive glomerular deposits of C3 and the terminal C5b-9 complement complex (TCC), but no immune complex deposits were detected by immunofluorescence in porcine membranoproliferative glomerulonephritis type II. TCC deposits were always observed with concomitant deposits of vitronectin (S-protein) in membranoproliferative glomerulonephritis, in contrast to a piglet with mesangial glomerulopathy where TCC was present without vitronectin co-deposition. Enzyme immunoassays revealed extensive systemic complement activation in 1-week-old affected piglets, observed by low plasma C3 (about 5% of normal) and high plasma TCC (about 10 x normal). Affected piglets revealed some plasma complement activation already at birth, 3 to 4 weeks before recognizable clinical disease. It is concluded that porcine membranoproliferative glomerulonephritis represents a nonimmune complex-mediated glomerulonephritis caused by unrestricted systemic complement activation with C3 consumption, TCC formation, and glomerular trapping of complement activation products. A pathogenetic mechanism of a defective or missing complement regulation protein is suggested.
Jansen
J H
JH
Department of Morphology, Norwegian College of Veterinary Medicine, Oslo.
Høgåsen
K
K
Mollnes
T E
TE
D000818:Animals; D003176:Complement C3 / Q000032:analysis* / Q000276:immunology / Q000652:urine; D015938:Complement Membrane Attack Complex / Q000032:analysis* / Q000276:immunology / Q000652:urine; D003429:Cross Reactions / Q000276:immunology*; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D015432:Glomerulonephritis, Membranoproliferative / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007678:Kidney Glomerulus / Q000737:chemistry*; D013552:Swine
D003176:Complement C3; D015938:Complement Membrane Attack Complex