Disease-associated loss of erythrocyte complement receptors (CR1, C3b receptors) in patients with systemic lupus erythematosus and other diseases involving autoantibodies and/or complement activation.
Disease-associated loss of erythrocyte complement receptors (CR1, C3b receptors) in patients with systemic lupus erythematosus and other diseases involving autoantibodies and/or complement activation.
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DOI：
10.4049/jimmunol.135.3.2005
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发表时间：
1985-09
影响因子：
4.4
通讯作者：
G. D. Ross;William J. Yount;M. Walport;J. Winfield;Charles J. Parker;C. Fuller;Ronald P. Taylor;B. Myones;Peter J. Lachmann
中科院分区：
文献类型：
--
作者：
G. D. Ross;William J. Yount;M. Walport;J. Winfield;Charles J. Parker;C. Fuller;Ronald P. Taylor;B. Myones;Peter J. Lachmann
虽然红细胞表面补体受体1型(CR1)的膜密度可能是正常人的遗传特征，但我们实验室最近的证据表明，系统性红斑狼疮(SLE)患者红细胞补体受体1型(CR1)的减少是后天因素和遗传因素共同作用的结果。本文用~(125)I-抗CR1单抗对SLE患者每例E的CR1数量进行了定量，发现在连续随访长达14个月的SLE患者中，CR1的数量与疾病活动性成反比。虽然没有证据表明E表面结合的免疫复合体或固定的C3b/iC3b，但疾病活动期和每E低数量的CR1与每E存在100至800个固定C3dg片段的分子有关(正常受试者每E少于100 C3dg)。在其他与补体激活相关的疾病，包括慢性冷凝集素病、自身免疫性溶血性贫血、阵发性睡眠性血红蛋白尿(PNH)、干燥综合征和支原体肺炎的患者中，也观察到CR1减少和E上过量的固定C3dg。经回归分析，CR1/E与固定C3dg/E呈显著负相关(r=-0.498)。活动期CR1降低，固定性C3dG升高，缓解期则相反。活动期SLE患者血清补体活性和E-CR1均降低，而固定C3dg片段增加。通过分段线性回归分析，患者E上出现100~400C3dg分子对应于每个E上CR1的数量减少了27%~60%(p<0.0002)，证实了C3对E的固定与CR1的丢失有关。在PNH患者中，中度补体敏感的PNH IIE的CR1值较低，伴随着固定C3片段的增加；然而，显著补体敏感的PNH IIIE型的CR1基本正常，几乎没有固定的C3。将可溶性DNA/抗DNA免疫复合体加入到正常血液中，E上产生的固定C3dg片段水平与SLE患者E上观察到的水平相当。动力学实验表明，在免疫复合物结合和从E-CR1释放的过程中，C3b被固定在E上，随后这种固定的C3b迅速降解为固定的C3b，更慢地降解为固定的C3dg，而不会像体内发生的CR1丢失。
Although surface membrane density of complement receptor type one (CR1) on erythrocytes (E) is probably an inherited trait among normal individuals, recent evidence from our laboratories suggests that the reduced number of CR1 per E observed in patients with systemic lupus erythematosus (SLE) results from acquired as well as genetic factors. In the present investigation, the number of CR1 per E was quantitated with 125I-monoclonal anti-CR1 and was found to vary inversely with disease activity in patients with SLE who were followed serially for as long as 14 mo. Although evidence for E surface-bound immune complexes or fixed C3b/iC3b was not obtained, periods of disease activity and low amounts of CR1 per E correlated with the presence of 100 to 800 molecules per E of fixed C3dg fragments (less than 100 C3dg per E in normal subjects). Reduced CR1 and excess fixed C3dg on E also were observed in patients with other disorders associated with complement activation, including chronic cold agglutinin disease, autoimmune hemolytic anemia, paroxysmal nocturnal hemoglobinuria (PNH), Sjögren's syndrome, and mycoplasma pneumonia. A significant negative correlation (r = -0.498) between CR1/E and fixed C3dg/E was demonstrable in 255 individual assays evaluated by regression analysis. CR1 decreased and fixed C3dg increased during active disease; the converse was obtained during remission. In patients with active SLE, both serum complement activity and E CR1 decreased, whereas fixed C3dg fragments increased. By piecewise linear regression analysis, the appearance of 100 to 400 C3dg molecules on patients' E corresponded to a 27 to 60%, reduction in the number of CR1 per E (p less than 0.0002), confirming that fixation of C3 to E was correlated with a loss of CR1. In patients with PNH, low values for CR1 were observed on moderately complement-sensitive PNH type II E in association with increased fixed C3 fragments; however, the markedly complement-sensitive PNH type III E had essentially normal amounts of CR1 and bore little fixed C3. The addition of soluble DNA/anti-DNA immune complexes to normal blood generated levels of fixed C3dg fragments on E comparable to those observed on E from patients with SLE. Kinetic experiments indicated that C3b was fixed to E during the process of immune complex binding and release from E CR1, and that this fixed C3b was subsequently degraded rapidly to fixed iC3b and more slowly to fixed C3dg without the loss of CR1 that occurs in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)