Salmon Jane E, Girardi Guillermina
Department of Medicine, Hospital for Special Surgery-Weill Medical College of Cornell University, New York, N.Y., USA.
Curr Dir Autoimmun. 2004;7:133-48. doi: 10.1159/000075690.
The anti-phospholipid syndrome (APS) is characterized by recurrent fetal loss, vascular thrombosis and thrombocytopenia occurring in the presence of antiphospholipid (aPL) antibodies. We hypothesized that aPL antibodies activate complement in the placenta, generating split products that mediate placental injury and lead to fetal loss and growth restriction, and that complement activation by aPL antibodies in other vascular areas causes inflammation and thrombophilia. Here we review studies in a murine model of APS in which human aPL antibodies are passively transferred into pregnant mice. Blockade of complement activation using a C3 convertase inhibitor or genetic deletion of C3 protected mice from pregnancy complications induced by aPL antibodies. These findings demonstrate that complement activation is a central mechanism in aPL antibody-induced pregnancy loss and fetal growth restriction. Although the cause of tissue injury in APS is likely to prove multifactorial, we have shown that complement activation is an absolute requirement for the most serious phenotypic outcomes, pregnancy complications and thrombosis, and, therefore, that this pathway acts upstream of other important effector mechanisms.
抗磷脂综合征（APS）的特征是在抗磷脂（aPL）抗体存在的情况下出现反复流产、血管血栓形成和血小板减少。我们推测，aPL抗体在胎盘中激活补体，产生介导胎盘损伤并导致流产和生长受限的裂解产物，并且aPL抗体在其他血管区域激活补体可引起炎症和血栓形成倾向。在此，我们综述了在一种APS小鼠模型中的研究，该模型将人aPL抗体被动转移到怀孕小鼠体内。使用C3转化酶抑制剂阻断补体激活或通过基因敲除C3可保护小鼠免受aPL抗体诱导的妊娠并发症。这些发现表明，补体激活是aPL抗体诱导的流产和胎儿生长受限的核心机制。尽管APS中组织损伤的原因可能是多因素的，但我们已经表明，补体激活是最严重表型结果、妊娠并发症和血栓形成的绝对必要条件，因此，该途径在其他重要效应机制的上游起作用。
