Burwick Richard M, Java Anuja, Regal Jean F
Maternal Fetal Medicine, San Gabriel Valley Perinatal Medical Group, Pomona Valley Hospital Medical Center, Pomona, CA, United States.
Division of Nephrology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States.
Front Immunol. 2025 Jul 24;16:1643896. doi: 10.3389/fimmu.2025.1643896. eCollection 2025.
Preeclampsia affects 3-4% of pregnancies with adverse effects for both mother and child. Minimal therapeutic options are available, and biomarkers are urgently needed to identify those at greatest risk early in the pregnancy. Both the innate and adaptive immune systems are well regulated during normal pregnancy including the complement system. A functioning complement system with some degree of complement activation participates in proper placental development, ensuring a healthy pregnancy and assisting with host defense. However, aberrant complement activation can lead to adverse pregnancy outcomes such as preeclampsia. An overview of the complement system will be presented, along with review of the pre-clinical literature in animal models providing evidence for complement involvement in maintaining a normal pregnancy and contributing to symptoms of preeclampsia. In addition, clinical studies with evaluation of complement biomarkers in plasma and urine implicate complement dysregulation in the pathophysiology of subtypes of preeclampsia including HELLP (hemolysis, elevated liver enzymes and low platelet count) syndrome. Recent studies on the genetics of complement dysregulation in preeclampsia will be reviewed, along with updates on use of recently developed complement therapeutics. The potential utility of evaluating complement activation or manipulating complement during pregnancy will be discussed in view of the successful use of complement therapeutics in pregnancy in other immune diseases.
子痫前期影响3% - 4%的孕妇，对母婴均有不良影响。目前可用的治疗方案有限，迫切需要生物标志物来在妊娠早期识别出风险最高的人群。在正常妊娠期间，包括补体系统在内的先天性和适应性免疫系统均受到良好调节。具有一定程度补体激活的正常补体系统参与胎盘的正常发育，确保妊娠顺利进行并协助宿主防御。然而，补体的异常激活可导致不良妊娠结局，如子痫前期。本文将概述补体系统，并回顾动物模型的临床前文献，这些文献为补体参与维持正常妊娠及子痫前期症状的产生提供了证据。此外，评估血浆和尿液中补体生物标志物的临床研究表明，补体失调与包括HELLP（溶血、肝酶升高和血小板减少）综合征在内的子痫前期亚型的病理生理学有关。本文将回顾子痫前期补体失调遗传学的最新研究，以及最近开发的补体疗法的应用进展。鉴于补体疗法在其他免疫疾病妊娠中的成功应用，将讨论评估妊娠期间补体激活或操纵补体的潜在效用。
