ANTIPHOSPHOLIPID ANTIBODIES AND RECURRENT PREGNANCY LOSS

狼疮抗凝剂（LAC）是一种获得性免疫球蛋白 磷脂依赖性凝血试验抑制剂， 与复发性流产相关，早期和重度 妊娠高血压，胎儿宫内发育迟缓， 血小板减少症和深静脉和动脉血栓形成。 是 当患者的血浆表现出延长 体外磷脂依赖性凝血，未经校正 加入等量的正常血浆。 的抑制 凝血是通过自身抗体结合到 凝血酶原-凝血酶原酶复合物的磷脂部分; 因此，抗凝血剂被鉴定为抗磷脂抗体， （阿帕）。 其他抗磷脂抗体，如 抗心磷脂和磷脂酰丝氨酸，也已经被 与相同的临床问题相关，事实上， 与LAC相同。 关于这种病毒的特异性， 抗体或生殖的可能机制 失败 我们建议的目的是：1）为本地法律援助定性 和其他抗磷脂抗体，2）确定 LAC所针对的特定磷脂，以及3） 评估与LAC和阿帕相关的可能机制 流产 方法将包括阿帕分析 在酶免疫测定中使用血清学反应性的特异性， 薄层层析法纯化磷脂抗原 层析，已知的抗体的生产和使用 通过多克隆的色谱纯化 已知特异性的抗体或通过产生 单克隆人和小鼠单克隆抗体， 评价这些抗体对体外 前列环素和血栓素的产生及其在 小鼠和家兔妊娠丢失模型。

Lupus anticoagulant (LAC) is an acquired immunoglobulin inhibitor of phospholipid dependent coagulation tests that is associated with recurrent pregnancy loss, early and severe pregnancy-induced hypertension, intrauterine growth retardation, thrombocytopenia, and deep venous and arterial thrombosis. It is identified when the patient's plasma demonstrates prolongation of in vitro phospholipid-depencent coagulation, without correction by the addition of an equal volume of normal plasma. The inhibition of coagulation is by the binding of the autoantibody to the phospholipid portion of the prothrombin-prothrombinase complex; thus, the anitcoagulatn is identified as an antiphospholip antibody (APA). Other antibodies against phospholipids, such as antibodies against cardiolipin and phosphatidylserine, have also been associated with the same clinical problems, and may, in fact, be indentical with LAC. Very little is known about the specificity of the antibody or the possible mechanism(s) for reproductive failure. The aims of our proposal are: 1) to characterize LAC and other antibodies against phospholipids, 2) determine the specific phospholipid(s) against which LAC is directed, and 3) to evaluate the possible mechanism(s) of LAC- and APA- associated pregnancy loss. Methodology will include analysis of APA specificity using serologic reactivity in enzyme immunoassays, purification of the phospholipid antigen by thin-layer chromatography, the production and use of antibodies of know specificity either by chromatographic purification of polyclonal antibodies of known specificity or by the production of monoclonal human and mouse monoclonal antibodies, and the evaluation of the affects of these antibodies on in vitro prostacyclin and thromboxane generation and of their activities in mouse and rabbit models of pregnancy loss.