Hydroxychloroquine reduces binding of antiphospholipid antibodies to syncytiotrophoblasts and restores annexin A5 expression.
Hydroxychloroquine reduces binding of antiphospholipid antibodies to syncytiotrophoblasts and restores annexin A5 expression.
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DOI：
10.1016/j.ajog.2011.06.064
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发表时间：
2011-12
影响因子：
9.8
通讯作者：
Rand JH
中科院分区：
文献类型：
--
作者：
Wu XX;Guller S;Rand JH
抗体介导的膜联蛋白A5（AnxA5）抗凝屏障的破坏被认为是抗磷脂综合征的血栓形成机制。我们最近发现，抗疟疾药物羟氯喹，解离抗磷脂免疫复合物，并恢复AnxA5结合平面磷脂双分子层。使用定量免疫测定，我们证明了类似的影响BeWo滋养层。因此，我们研究了药物对人胎盘合胞体滋养层细胞（SCT）原代培养物中AnxA5定位的影响。激光共聚焦显微镜与计算机为基础的形态分析被用来定位AnxA5和抗磷脂抗体暴露于多克隆和单克隆抗磷脂和对照IgG的SCT。羟氯喹逆转抗磷脂抗体对SCT的影响，显着降低IgG结合和恢复AnxA5的表达。这些结果为羟氯喹对人胎盘SCT的这种作用提供了第一个形态学证据，并支持靶向抗磷脂抗体结合的新型治疗方法的可能性。
Antibody-mediated disruption of the annexin A5 (AnxA5) anticoagulant shield has been posited to be a thrombogenic mechanism in the antiphospholipid syndrome. We recently showed that the antimalarial drug, hydroxychloroquine, dissociates antiphospholipid immune complexes and restores AnxA5 binding to planar phospholipid bilayer. Using quantitative immunoassays, we demonstrated similar effects on BeWo trophoblasts. We therefore investigated the effects of the drug on localization of AnxA5 in primary cultures of human placental syncytiotrophoblasts (SCTs). Laser confocal microscopy with computer-based morphometric analysis was used to localize AnxA5 and antiphospholipid antibodies on SCTs exposed to polyclonal and monoclonal antiphospholipid and control IgGs. Hydroxychloroquine reversed the effects of the antiphospholipid antibodies on the SCTs by markedly reducing IgG binding and restoring AnxA5 expression. These results provide the first morphologic evidence for this effect of hydroxychloroquine on human placental SCTs and support the possibility of novel treatments that target antiphospholipid antibody binding.