The metabolism of C9 in normal subjects and in patients with autoimmune disease
The metabolism of C9 in normal subjects and in patients with autoimmune disease
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DOI：
10.1046/j.1365-2249.1996.d01-636.x
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发表时间：
1996-04-01
影响因子：
4.6
通讯作者：
Charlesworth, JA
中科院分区：
文献类型：
--
作者：
Greenstein, JD;Peake, PW;Charlesworth, JA
研究了8名健康受试者和9名自身免疫性疾病患者（包括7名系统性红斑狼疮（SLE）患者和1名系膜伊加肾病和1名混合型原发性冷球蛋白血症患者）的补体第九组分（C9）代谢。在正常受试者中，代谢参数（平均值+/- s.d.）为：分解率分数（FCR）：2.92 +/- 0.36%/h，血浆半衰期（T-1/2）：42.5 +/- 6.7 h，血管外/血管内分布比（EV/IV）：0.56 +/- 0.12。在患者中，FCR为3.38 +/- 0.70%/h，T-1/2为37.6 +/- 10.2 h，EV/IV为0.55 +/- 0.19。与对照组相比，总血清溶血活性降低的患者（即CH 50 <正常人血清（NHS）的68%，n = 7）具有显著更高的FCR（3.57 = 0.67%/h）和更短的T-1/2（33.5 +/- 6.8 h）（均P < 0.05）。患者的终末补体复合物（即可溶性TCC或SC 5 b-9）的血浆浓度（中位数（范围）：515（300-1879 μ g/l））高于正常受试者（313（229-402 μ g/l）; P < 0.01），并与C9的FCR呈正相关（r = 0.61，P < 0.01）。患者血浆C9生成率（0.11 +/- 0.05 mg/kg/h）也高于对照组（0.07 +/- 0.03 mg/kg/h，P < 0.05），并且与患者血清中较高的C9浓度相关（76 +/- 13 mg/l vs 61 +/- 14 mg/l，P < 0.05）。这些结果表明，C9在正常人中被快速代谢，并且在患有自身免疫性疾病和补体激活的患者中发生高催化活性。尽管存在正常或升高的血清C9水平和正常房室分布，但仍存在这种情况。
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 (T-1/2): 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 T-1/2 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 T-1/2 (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 mu g/l)) than in normal subjects (313 (229-402 mu g/l); 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.