Di Simone N, Meroni P L, D'Asta M, Di Nicuolo F, D'Alessio M C, Caruso A
Department of Obstetrics and Gynecology, Catholic University of Sacred Heart, Rome.
Hum Reprod Update. 2007 Mar-Apr;13(2):189-96. doi: 10.1093/humupd/dml051. Epub 2006 Nov 11.
Most of the clinical manifestations of the antiphospholipid syndrome (APS) can be related to thrombotic events; however, placental thrombosis cannot explain all of the pregnancy complications that occur in women with this syndrome. In this regard, it has been hypothesized that antiphospholipid (aPL) antibodies can directly attack trophoblasts, but it is still unclear what pathogenetic mechanisms play a role and which aPL antibodies subpopulations are involved. Although it has been assumed that aPL antibodies are directed against anionic phospholipids (PLs), current advances in the field suggest that antibodies to PL-binding plasma protein such as beta2-glycoprotein-I (beta2-GPI) are the clinically relevant aPL antibodies. It appears that following the attachment of beta2-GPI to PLs, both molecules undergo conformational changes that result in the exposure of cryptic epitopes within the structure of beta2-GPI allowing the subsequent binding of antibodies. aPL antibodies detected by anti-beta2-GPI assays are associated with fetal loss. However, there is still debate on how the antibodies might induce the obstetrical manifestations. The significantly improved outcome of pregnancies treated with heparin has stimulated interest in the drug's mechanisms of action. Several mechanisms could explain its beneficial effects, because in addition to a direct effect of heparin on the coagulation cascade, it might protect pregnancies by reducing the binding of aPL antibodies, reducing inflammation, facilitating implantation and/or inhibiting complement activation. Further investigations are needed to better understand how aPL antibodies induce obstetric complications and to better clarify the functional role of heparin in the human placenta leading to more successful therapeutic options.
抗磷脂综合征（APS）的大多数临床表现都可能与血栓形成事件有关；然而，胎盘血栓形成并不能解释该综合征女性所发生的所有妊娠并发症。在这方面，有人提出抗磷脂（aPL）抗体可直接攻击滋养层细胞，但仍不清楚哪些致病机制起作用以及涉及哪些aPL抗体亚群。尽管一直认为aPL抗体是针对阴离子磷脂（PLs）的，但该领域的当前进展表明，针对PL结合血浆蛋白如β2-糖蛋白-I（β2-GPI）的抗体才是临床上相关的aPL抗体。似乎在β2-GPI与PLs结合后，这两种分子都会发生构象变化，导致β2-GPI结构内隐蔽表位暴露，从而允许抗体随后结合。通过抗β2-GPI检测法检测到的aPL抗体与胎儿丢失有关。然而，关于这些抗体如何诱导产科表现仍存在争议。肝素治疗的妊娠结局显著改善，激发了人们对该药物作用机制的兴趣。有几种机制可以解释其有益作用，因为除了肝素对凝血级联的直接作用外，它可能通过减少aPL抗体的结合、减轻炎症、促进着床和/或抑制补体激活来保护妊娠。需要进一步研究以更好地理解aPL抗体如何诱导产科并发症，并更好地阐明肝素在人胎盘中的功能作用，从而带来更成功的治疗选择。
