Hereditary porcine membranoproliferative glomerulonephritis type II is caused by factor H deficiency.
We have recently described hereditary membranoproliferative glomerulonephritis type II in the pig. All affected animals had excessive complement activation, revealed as low plasma C3, elevated plasma terminal complement complex, and massive deposits of complement in the renal glomeruli, and eventually died of renal failure within 11 wk of birth. The aim of the present study was to investigate the cause of complement activation in this disease. Transfusion of normal porcine plasma to affected piglets inhibited complement activation and increased survival. Plasma was successively fractionated and the complement inhibitory effect of each fraction tested in vivo. A single chain 150-kD protein which showed the same complement inhibitory effect as whole plasma was finally isolated. Immunologic cross-reactivity, functional properties, and NH2-terminal sequence identified the protein as factor H. By Western blotting and enzyme immunoassay, membranoproliferative glomerulonephritis-affected piglets were demonstrated to be subtotally deficient in factor H. At 1 wk of age, median (range) factor H concentration was 1.6 mg/liter (1.1-2.3) in deficient animals (n = 13) and 51 mg/liter (26-98) in healthy littermates (n = 52). Our data show that hereditary porcine membrano-proliferative glomerulonephritis type II is caused by factor H deficiency.
Høgåsen
K
K
Institute of Immunology and Rheumatology, National Hospital, University of Oslo, Norway.
Jansen
J H
JH
Mollnes
T E
TE
Hovdenes
J
J
Harboe
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001323:Autoantibodies / Q000032:analysis; D001803:Blood Transfusion; D015153:Blotting, Western; D017242:Complement Factor H / Q000737:chemistry / Q000172:deficiency* / Q000276:immunology / Q000302:isolation & purification; D015938:Complement Membrane Attack Complex; D003170:Complement Pathway, Alternative; D003165:Complement System Proteins / Q000032:analysis; D004195:Disease Models, Animal; D015432:Glomerulonephritis, Membranoproliferative / Q000209:etiology* / Q000235:genetics; D007124:Immunoenzyme Techniques; D007674:Kidney Diseases / Q000151:congenital*; D008969:Molecular Sequence Data; D017421:Sequence Analysis; D013552:Swine
D001323:Autoantibodies; D015938:Complement Membrane Attack Complex; C058872:complement 4 nephritic factor; D017242:Complement Factor H; D003165:Complement System Proteins