Analysis of thrombosis formation in patients with antiphospholipid syndrome

抗磷脂抗体(抗心磷脂抗体；前交叉韧带和狼疮抗凝剂；LA)的存在与血栓栓塞症、胎儿宫内丢失和血小板减少有关。术语抗磷脂综合征(APS)被用来定义这一组病理特征，该综合征的临床特征是基于抗磷脂介导的促凝状态。在本研究中，我们研究了aPS患者抗磷脂抗体，特别是acl的精确特征，得到了以下结果：1)aPS患者acl与β2-糖蛋白I(beta2-gpi)结构上的隐含表位(S)相互作用时，β2-gpi与聚氧磷脂板以及由带负电荷的磷脂(如心磷脂和磷脂酰丝氨酸)组成的脂膜相互作用；2)基于上述观察，我们建立了一种新的准确检测acl的方法，使用涂有beta2-gpi的聚氧聚苯乙烯板，而不是CL包被的板。3)利用新开发的β_2-GPI缺失突变体和结构域特异性抗β_2-GPI单抗，研究了β_2-GPI的体外生物学意义。4)我们发现β_2-GPI与oxLDL结合并抑制巨噬细胞对oxLDL的体外摄取。相反，同时加入人β2-GPI和单克隆性ACL可显著增加oxLDL的结合。

The presence of antiphospholipid antibodies (anticardiolipin antibodies ; aCL and lupus anticoagulants ; LA) is associated with thromboembolic manifestations, intrauterine fetal loss and thrombocytopenia. The term antiphospholipid syndrome (APS) has been used to define this set of pathologic trait, and the clinical feature of this syndrome is based on the antiphospholpid-mediated procoagulant state. In the present study, we investigated the precise characteristic of antiphospholpid antibodies, especially aCL from patients with APS and obtained following results.1) aCL from patients with APS recognized cryptic epitope (s) appearing on the beta2-glycoprotein I (beta2-GPI) structure when beta2-GPI interacts with polyoxygenated polystirene plates as well as with lipid membranes composed of negatively-charged phospholpids such as cardiolipin and phosphatidylserine.2) Based on the observation described above, we established a novel and accurate assay (ELISA) method for aCL using polyoxygenated polystirene plates coated with beta2-GPI,instead of CL-coated plates, and clarified the clinical significance of this system.3) We investigated the biological significance of beta2-GPI in vitro, by using newly developed deletion mutants of beta2-GPI,and domain specific anti- beta2-GPI monoclonal antibodies.4) We found that beta2-GPI bound to oxLDL and inhibited in vitro uptake of oxLDL by macrophages. Conversely, the binding of oxLDL was significantly increased by the simultaneous addition of human beta2-GPI and monoclonal aCL.