LUPUS ANTICOAGULANT AND RECURRENT PREGNANCY LOSS

狼疮抗凝剂与复发性流产

• 批准号: 3320405
• 负责人: DAVID WARE BRANCH
• 金额: $ 11.41万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-04-01 至 1989-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3320405
• 关键词: affinity chromatography; antigens; autoantibody; enzyme linked immunosorbent assay; gestational age; human subject; human tissue; immunization; immunoglobulin G; immunoglobulin M; phosphatidylserines; phospholipids; pregnancy immunology; prostacyclins; radioimmunoassay; spontaneous abortion; thromboplastin

Lupus anticoagulant (LAC) is an autoantibody that is associated with recurrent first-trimester abortion and second-trimester fetal death, with 80% or more of pregnancies in women with the anticoagulant ending in fetal wastage. In pregnancies that progress beyond mid-gestation, severe or early preeclampsia and fetal growth retardation are common. LAC is commonly detected by its prolongation-effect on phospholipid-dependent coagulation, and the antibody has been identified as an anti-phospholipid. The pathophysiologic effect of LAC has been attributed to the inhibition of vascular prostacyclin production that has been observed in vitro in the presence of the antibody. We propose to study two aspects of LAC. First, we will evaluate the specific antigen-antibody interactions for LAC using an immunologic assay that we have developed. Our preliminary results suggest that the antigen is the phospholipid, phosphatidylserine. Secondly, we will study the mechanism of LAC using a prostacyclin generation assay and mouse and rabbit models of reproduction. The animals will be actively immunized with various phospholipid preparations or passively immunized with purified human LAC preparations or human or mouse monoclonal LAC, and their reproductive performance evaluated.

狼疮抗凝剂（LAC）是一种自身抗体， 妊娠早期反复流产和妊娠中期胎儿死亡， 80%或更多的妊娠妇女的抗凝剂终止于胎儿 浪费 在妊娠中期以后的妊娠中，重度或 早期先兆子痫和胎儿生长迟缓是常见的。 LAC是 通常通过其对磷脂依赖性 凝血，并且该抗体已被鉴定为抗磷脂。 LAC的病理生理效应归因于抑制 血管前列环素的产生已经在体外观察到， 抗体的存在。 我们建议研究两方面的问题。 第一、 我们将使用以下方法评估LAC的特异性抗原-抗体相互作用： 我们开发的一种免疫检测方法。 我们的初步结果 表明抗原是磷脂，磷脂酰丝氨酸。 其次，我们将研究使用前列环素的LAC的机制 代测定以及小鼠和兔繁殖模型。 动物 将用各种磷脂制剂主动免疫，或 用纯化的人LAC制剂或人或小鼠被动免疫 单克隆LAC，并评价其繁殖性能。