Salmon Jane E, Girardi Guillermina
Department of Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA.
Trans Am Clin Climatol Assoc. 2007;118:99-114.
The antiphospholipid syndrome (APS), characterized by thrombosis and pregnancy loss that occur in the presence of antiphospholipid (aPL) antibodies, is a leading cause of miscarriage and maternal and fetal morbidity. Using a mouse model of APS induced by passive transfer of human aPL antibodies, we have shown that complement activation plays an essential and causative role in pregnancy loss and fetal growth restriction, and that blocking activation of the complement cascade rescues pregnancies. Given that the primary treatment for APS patients is anticoagulation throughout pregnancy, usually with sub-anticoagulant doses of heparin, we considered the possibility that heparin prevents pregnancy loss by inhibiting complement. We found that heparin inhibits activation of complement on trophoblasts in vivo and in vitro and that anticoagulation, in and of itself, is not sufficient to prevent pregnancy complications in our experimental model of APS. Our studies underscore the importance of inflammation in fetal injury associated with aPL antibodies and emphasize the importance of developing and testing targeted complement inhibitory therapy for patients with APS.
抗磷脂综合征（APS）以在抗磷脂（aPL）抗体存在的情况下发生血栓形成和流产为特征，是流产以及母婴发病的主要原因。利用通过被动转移人aPL抗体诱导的APS小鼠模型，我们已经表明补体激活在流产和胎儿生长受限中起重要的致病作用，并且阻断补体级联反应的激活可挽救妊娠。鉴于APS患者的主要治疗方法是在整个孕期进行抗凝，通常使用低于抗凝剂量的肝素，我们考虑了肝素通过抑制补体来预防流产的可能性。我们发现肝素在体内和体外均可抑制滋养层细胞上补体的激活，并且在我们的APS实验模型中，抗凝本身不足以预防妊娠并发症。我们的研究强调了炎症在与aPL抗体相关的胎儿损伤中的重要性，并强调了为APS患者开发和测试靶向补体抑制疗法的重要性。
