INTERVENTION OF AUTOANTIBODY IN THE MEMBRANE PHOSPHOLIPID FLIP-FLOP OF TROPHOBLAST CELLS.

抗磷脂抗体是一种与抗磷脂综合征（APS）相关的自身抗体，APS表现为动脉和静脉血栓形成、血小板减少症和复发性胎儿丢失。这些并发症的潜在机制尚不完全清楚，而它们显然是由于加速凝血。由于带负电荷的磷脂磷脂酰丝氨酸在细胞凋亡和滋养细胞分化过程中暴露于质膜外小叶，可能引发血液凝固，因此我们将重点放在与带负电荷的磷脂结合的蛋白质上，以描述APS的发病机制。制备亲和柱，将心磷脂或磷脂酰丝氨酸包埋于辛基纤维素中，用2M NaCl洗脱，收集与这些磷脂结合的血浆蛋白。A蛋白通过iD或2D电泳分离，再通过肽质量指纹图谱进行鉴定。这些蛋白包括β 2糖蛋白I、α -胰蛋白酶抑制剂家族重链相关蛋白（IHRP）、补体因子4、因子H和因子H相关蛋白I。因子H的结合是有趣的，因为因子H突变导致溶血性尿毒症综合征，其特征病理为肾微血管血栓形成，APS也会发生。最近，替代补体通路激活的关键作用已被报道。因此，可能涉及因子H，一种替代途径的调节蛋白，将是描述APS发病机制的一个有吸引力的推测。

Antiphospholipid antibody is an autoantibody associated with antiphospholipid syndrome (APS) representing arterial and venous thrombosis, thrombocytopenia, and recurrent fetal loss. The underlying mechanism of these complications is not fully understood, while they are obviously due to accelerated coagulation. Since a negatively charged phospholipid, phosphatidylserine, which potentially triggers blood coagulation, is exposed to the outer leaflet of plasma membrane during apoptosis and trophoblast differentiation, we focused on the proteins binding to negatively charged phospholipids in order to delineate the pathogenesis of APS. An affinity column, in which cardiolipin or phosphatidylserine was embedded in octyl cellulose was prepared, and the plasma proteins bound to these phospholipids were collected by elution with 2M NaCl. A proteins were separated by iD or 2D electrophoresis, and then identified by peptide mass fingerprinting. The proteins included beta2 glycoprotein I, inter-alpha-trypsin inhibitor family heavy chain-related protein (IHRP), complement factor 4, factor H and factor H-related protein I. The binding of factor H was interesting, since factor H mutations cause hemolytic uremic syndrome with characteristic pathology of renal microvascular thrombosis, which also occurs in APS. Recently, the crucial role of alternative complement pathway activation has been reported. Thus, possible involvement of factor H, a regulatory protein of alternative pathway, would be an attractive speculation to delineate the pathogenesis of APS.