First Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary.
Mol Immunol. 2010 Apr;47(7-8):1500-6. doi: 10.1016/j.molimm.2010.01.021. Epub 2010 Feb 23.
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 C1-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.
本研究旨在全面探讨补体系统在正常妊娠和子痫前期中的作用，通过酶联免疫吸附试验、放射免疫扩散法和粒子增强免疫比浊法测定补体蛋白、其激活片段和调节因子以及 C 反应蛋白（CRP）的循环水平。本病例对照研究纳入了 60 例子痫前期患者、60 例健康孕妇和 59 名健康未孕妇女。CRP、C4d、C3a、SC5b9、C3、C9 和 FH 抗原水平显著高于健康未孕妇女，而 C1 抑制剂水平显著低于健康未孕妇女。此外，子痫前期患者的 CRP、C4d、C3a、SC5b9 水平显著高于健康孕妇，C3 浓度显著低于健康孕妇。与健康孕妇相比，其 CRP、C4d、C3a、SC5b9、C4、C3、C9 和 FH 抗原水平显著升高，而 C1 抑制剂浓度显著降低。然而，三组研究对象的 Bb 和 C4b 结合蛋白水平无显著差异。伴有胎儿生长受限的子痫前期患者的血浆 SC5b9 水平显著高于无 IUGR 的患者。在正常妊娠和子痫前期中，C1 抑制剂和 C4b 结合蛋白相对缺乏，而 FH 相对丰富。经典或凝集素途径的激活（C4d）与健康孕妇和子痫前期患者的 C3 激活（C3a）呈显著正相关。然而，仅在子痫前期患者中，末端途径的激活与 C3 的相关性占主导地位，而在健康孕妇中并非如此。总之，在正常妊娠的第三个三个月，补体系统通过经典和/或凝集素途径激活，末端复合物形成增加，在子痫前期中进一步激活，这表现在循环系统中激活标志物的数量增加。末端途径的过度激活与子痫前期患者的胎儿生长受限有关。然而，还需要进一步的研究来确定这种妊娠特有的疾病中全身补体激活的原因和后果。
