The metabolism of C9 in normal subjects and in patients with autoimmune disease.
The metabolism of the ninth component of complement (C9) was studied in eight healthy subjects and nine patients with autoimmune disease, including seven with systemic lupus erythematosus (SLE) and one each with mesangial IgA nephropathy and mixed essential cryoglobulinaemia. In normal subjects the metabolic parameters(mean +/- s.d.) were : fractional catabolic rate (FCR): 2.92 +/- 0.36%/h, plasma half-life (T1/2): 42.5 +/- 6.7 h, and extravascular/intravascular distribution ratio (EV/IV): 0.56 +/- 0.12. In patients the FCR was 3.38 +/- 0.70%/h, the T1/2 was 37.6 +/- 10.2 h, and the EV/IV was 0.55 +/- 0.19. Patients with reduced total serum haemolytic activity (i.e. CH50 <68% of normal human serum (NHS), N=7) had significantly higher FCR (3.57 +/- 0.67%/h) and shorter T1/2(33.5 +/- 6.8 h) than the control group (both P<0.05). The plasma concentration of the terminal complement complex (i.e. soluble TCC or SC5b-9) was higher in patients (median (range): 515 (300-1879 micrograms/l) than in normal subjects (313 (229-402 micrograms/liters): P<0.01) and showed a positive correlation with the FCR of C9 (r=0.61, P<0.01). Plasma C9 production rate was also greater in patients (0-11 +/- 0-05 mg/kg per h) compared with control subjects (0-07 +/- 0.03 mg/kg per h, P<0.05), and was associated with a higher C9 concentration in patients' sera (76 +/- 13 mg/l versus 61 +/- 14 mg/l, P<0.05). These results demonstrate that C9 is rapidly metabolized in normal humans and that hypercatabolism occurs in patients with autoimmune disease and complement activation. This was despite the presence of normal or elevated serum C9 levels and normal compartmental distribution.
Greenstein
J D
JD
Department of Nephrology, Prince Henry Hospital, Little Bay, NSW, Australia.
Peake
P W
PW
Charlesworth
J A
JA
D000328:Adult; D001327:Autoimmune Diseases / Q000276:immunology*; D003167:Complement Activation; D003186:Complement C9 / Q000378:metabolism*; D015938:Complement Membrane Attack Complex; D003165:Complement System Proteins / Q000378:metabolism; D003449:Cryoglobulinemia / Q000276:immunology*; D005260:Female; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008297:Male; D008657:Metabolic Clearance Rate
D003186:Complement C9; D015938:Complement Membrane Attack Complex; D006023:Glycoproteins; C047610:SC5b-9 protein complex; D003165:Complement System Proteins