Activation of the complement system in normal pregnancy and preeclampsia
Activation of the complement system in normal pregnancy and preeclampsia
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DOI：
10.1016/j.molimm.2010.01.021
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发表时间：
2010-04-01
影响因子：
3.6
通讯作者：
Molvarec, Attila
中科院分区：
文献类型：
--
作者：
Derzsy, Zoltan;Prohaszka, Zoltan;Molvarec, Attila
本研究的目的是探讨补体系统在正常人妊娠和先兆子痫中的作用，以全面的方式，测量循环水平的补体蛋白，其活化片段和调节因子，以及C-反应蛋白（CRP）。选择60例子痫前期患者、60例健康孕妇和59例健康非孕妇女作为对照组。采用ELISA法、放射免疫扩散法和微粒增强免疫比浊法测定循环中补体成分和CRP水平。健康孕妇CRP、C4d、C3 a、SC 5 b 9、C3、C9和H因子抗原水平显著高于非孕妇，而C1抑制物水平显著低于非孕妇。此外，与健康孕妇相比，先兆子痫患者具有显著较高的CRP、C4d、C3 a、SC 5 b 9水平和显著较低的C3浓度。他们的CRP，C4d，C3 a，SC 5 b 9，C4，C3，C9和因子H抗原水平显着较高，而Cl-抑制剂浓度显着低于健康非妊娠妇女。然而，三个研究组之间没有发现Bb和C4 b结合蛋白水平的显著差异。先兆子痫患者胎儿生长受限的血浆SC 5 b 9水平显着高于那些没有IUGR。在正常妊娠和子痫前期患者中，C1抑制物和C4 b结合蛋白相对缺乏，而H因子相对丰富。在健康孕妇和先兆子痫患者中，经典或凝集素途径（C4d）的活化与C3活化（C3 a）均显示出显著的正相关性。然而，C3和终末通路激活之间的相关性仅在先兆子痫患者中占主导地位，而在健康孕妇中则不存在。总之，补体系统是通过经典和/或凝集素途径激活的，在正常人妊娠的第三个三个月，并进一步在先兆子痫中增加了末端复合物的形成，如体循环中激活标志物的量升高所示。终末通路的过度激活与先兆子痫妇女胎儿生长受限相关然而，需要进一步的研究来确定这种妊娠特异性疾病中全身性补体激活的原因和后果。(C)2010爱思唯尔有限公司保留所有权利。
The purpose of this study was to explore the role of the complement system in normal human pregnancy and preeclampsia in a comprehensive manner, measuring circulating levels of complement proteins, their activation fragments and regulatory factors, as well as those of C-reactive protein (CRP). Sixty preeclamptic patients, 60 healthy pregnant women and 59 healthy non-pregnant women were involved in this case-control study. Circulating levels of complement components and CRP were determined with ELISA, radial immunodiffusion and particle enhanced immunoturbidimetric assay. Levels of CRP, C4d, C3a, SC5b9, C3, C9 and factor H antigen were significantly higher, while those of C1-inhibitor were significantly lower in healthy pregnant than non-pregnant women. In addition, preeclamptic patients had significantly higher CRP, C4d, C3a, SC5b9 levels and significantly lower C3 concentrations as compared to healthy pregnant women. Their CRP, C4d, C3a, SC5b9, C4, C3, C9 and factor H antigen levels were significantly higher, while Cl-inhibitor concentrations were significantly lower compared with healthy non-pregnant women. However, no significant difference was found in Bb and C4b-binding protein levels among the three study groups. Preeclamptic patients with fetal growth restriction had significantly higher plasma SC5b9 levels than those without IUGR. There was a relative deficiency of C1-inhibitor and C4b-binding protein, and a relative abundance of factor H both in normal pregnancy and preeclampsia. Activation of the classical or lectin pathway (C4d) showed significant positive correlation to C3 activation (C3a) both in healthy pregnant women and preeclamptic patients. However, the correlation between C3 and terminal pathway activation was dominating only in patients with preeclampsia, but not in healthy pregnant women. In conclusion, the complement system is activated through the classical and/or lectin pathways with increased terminal complex formation in the third trimester of normal human pregnancy, and further in preeclampsia, as shown by the elevated amounts of activation markers in the systemic circulation. Excessive activation of the terminal pathway is associated with fetal growth restriction in preeclamptic women. However, additional studies are required to determine the cause and consequence of systemic complement activation in this pregnancy-specific disorder. (C) 2010 Elsevier Ltd. All rights reserved.