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系统性红斑狼疮(SLE)、抗磷脂抗体(APA)、 通过ELISA(抗心磷脂抗体，A C A)或通过 体外对磷脂依赖凝血的抑制作用 (狼疮抗凝剂，LAC)与复发密切相关 血栓形成、胎儿丧失、血小板减少和神经病理学( 抗磷脂综合征(APS)。当获得性凝血异常时 在没有系统性红斑狼疮的情况下发生的APS称为原发APS。至 目前，APA在APS免疫发病机制中的作用尚不清楚。 对APA的分析表明，它们是由免疫学和 在功能上不同的抗体种类。考虑到一些人 持续升高的血清ACA和LAC不会发生血栓形成 问题，我们假设只有APS患者中的某些APA可能会导致 血栓形成，这种致血栓的APA是必要的，但不是充分的 例如，诱发病理性血栓形成。潜在的血栓形成 抗体可能具有独特的结合特异性和亲和力 磷脂和/或辅因子(S)，目前的分析不欣赏 血浆样品中的多克隆异质性APA。为了检验这些假设， 我们计划： 1从血清效价高的APS患者中产生单抗Ig G APA APA和反复血栓形成，并表征结合的特异性 和单抗APA的亲和力； 2)体外测定单特异性APA的功能性质 小鼠凝血试验和体内血栓形成模型； 3)研究促血栓和抗凝血剂APA的作用机制 它们的影响； 这些研究的结果将有助于定义APA的不同子集 对反复血栓形成的APS患者的治疗，以提高我们的认识 APA在与APS相关的血栓形成中的作用。如果有些人 发现了致血栓形成的APA，其免疫学特征和 致病机制将被揭示。

In systemic lupus erythematosus (SLE), antiphospholipid antibodies (APA), detected either by ELISA (anticardiolipin antibodies, A C A) or by an inhibitory effect on phospholipid-dependent in vitro blood coagulation (lupus anticoagulant, LAC), are strongly associated with recurrent thrombosis, fetal loss, thrombocytopenia and neurological pathology (the "antiphospholipid syndrome" APS). When acquired coagulation abnormalities of APS occur in the absence of SLE, it is referred to as primary APS. To date, the role of APA in immunopathogenesis of APS remains unclear. Analyses of APA indicate that they are composed of immunologically and functionally distinct antibody species. Considering that some individuals with persistently elevated serum ACA and LAC do not experience thrombotic problems, we hypothesize that only certain APA in APS patients may cause thrombosis, and that such thrombogenic APA is necessary, but not sufficient for, induction of pathologic thrombosis. The potentially thrombogenic antibodies may possess unique binding specificity and affinity to phospholipid and/or cofactor(s), not appreciated with present analyses of polyclonal heterogeneous APA in plasma samples. To test these hypotheses, we plan to: 1 Generate monoclonal IgG APA from APS patients with high titers of serum APA and recurrent thrombosis, and characterize the binding specificities and affinities of the monoclonal APA; 2) Determine the functional properties of monospecific APA by in vitro blood clotting assays and an in vivo thrombosis model in mice; 3) Study the mechanisms by which thrombogenic and anticoagulant APA exert their effects; The results from these studies will help to define various subsets of APA in APS patients with recurrent thrombosis, and to advance our understanding about the role of APA in thrombosis associated with APS. If some thrombogenic APA are found, their immunological characteristics and pathogenic mechanisms will be revealed.