ANTIPHOSPHOLIPID ANTIBODIES AND RECURRENT PREGNANCY LOSS

狼疮抗凝剂(LAC)是一种获得性免疫球蛋白 磷脂依赖凝血试验的抑制物 与早期和严重的复发性妊娠丢失有关 妊娠高血压综合征，宫内发育迟缓， 血小板减少，以及深静脉和动脉血栓形成。它是 当患者的血浆表现出延长的时间 体外磷脂依赖凝血，不经 加入等量的正常血浆。抑制力 凝血的作用是通过自身抗体与 凝血酶原-凝血酶原酶复合体的磷脂部分； 因此，这种抗凝血素被鉴定为抗磷脂抗体。 (APA)。其他抗磷脂抗体，如抗体 抗心磷脂和磷脂酰丝氨酸，也 与相同的临床问题有关，而且实际上可能是 与LAC背道而驰。我们对它的特殊性知之甚少 生殖功能的抗体或可能机制(S) 失败了。我们建议的目的是：1)描述LAC的特征 和其他抗磷脂抗体，2)决定 LAC所针对的特定磷脂(S)，以及3) 评估LAC和APA相关的可能机制(S) 妊娠丢失。方法论将包括对APA的分析 在酶免疫分析中使用血清反应性的特异性， 薄层分离法纯化磷脂抗原 层析，已知抗体的产生和使用 通过层析纯化多克隆的特异性 已知的特异性抗体或通过产生 人和鼠的单抗，以及 评价这些抗体对体外培养细胞的影响 前列环素和血栓素的产生及其活性 小鼠和兔妊娠丢失模型的建立。

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.