ANTICARDIOLIPIN ANTIBODIES, BETA 2GI AND THROMBOSIS

抗心磷脂抗体、β2GI 和血栓形成

• 批准号: 2415601
• 负责人: SANDOR S SHAPIRO
• 金额: $ 30.53万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-05-01 至 1999-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2415601
• 关键词: anticoagulants; cardiolipins; chemical binding; disease /disorder model; disease /disorder proneness /risk; enzyme complex; enzyme linked immunosorbent assay; epitope mapping; glycoprotein structure; glycoproteins; human subject; immunoglobulins; intermolecular interaction; laboratory mouse; laboratory rabbit; molecular site; monoclonal antibody; mutant; phospholipids; protein sequence; protein structure function; synthetic peptide; systemic lupus erythematosus; thrombosis

Lupus anticoagulants (LACs) and anticardiolipin antibodies (ACAs) are defined as immunoglobulins reactive directly against anionic phospholipids, or having a requirement for anionic phospholipids for their reactivity. LACs are recognized by their prolongation of phospholipid- dependent coagulation tests, while ACAs are generally measured in ELISA assays. Although LACs and ACAs are related phenomena, there is reason to believe that these two activities frequently reside in separate immunoglobulin subpopulations. Nevertheless, the presence of either phenomenon is associated with an increased risk of thrombosis, spontaneous abortion (in women of child-bearing age), thrombocytopenia, as well as several other manifestations that have sometimes been referred to collectively as the "antiphospholipid antibody syndrome". Since the discovery that beta2-glycoprotein l (beta2Gl) is a necessary component in the reactivity of the majority of ACAs and, possibly, LACs, the nature of the interaction of these antibodies with beta2Gl, with phospholipid, and with the beta2Gl-phospholipid complex has assumed major importance. The aims of this proposal are: 1) To identify the specific areas and critical amino acid residues in beta2Gl involved in binding of cardiolipin (CL) and other anionic phospholipids. 2) To identify the epitopes in beta2Gl, CL, and the beta2Gl-CL complex to which LACs/ACAs bind. 3) To study the functional characteristics of epitope-specific LAC/ACA subpopulations, and to correlate epitope-specificities with the risk of thrombosis. These studies will make use of expression mutants of beta2Gl, monoclonal antibodies to beta2Gl, synthetic peptides mimicking surface characteristics of the beta2Gl molecule, and an animal thrombosis model in which to test the thrombogenic potential of antibody subpopulations. We believe that an understanding of the assembly of the beta2Gl-CL complex and the isolation and determination of the functional characteristics of epitope-specific subpopulations of LACs/ACAs will lead to a better understanding of the mechanisms giving rise to the thromboembolic risk and other clinical manifestations associated with the presence of these antibodies.

狼疮抗凝剂（拉克）和抗心磷脂抗体（ACA）是 定义为免疫球蛋白直接与阴离子 磷脂，或需要阴离子磷脂用于其 反应性拉克通过延长磷脂- 依赖性凝血试验，而ACA通常在ELISA中测量 分析。虽然拉克和ACA是相关的现象，但有理由 我认为这两种活动经常是分开的， 免疫球蛋白亚群。然而，无论是 这种现象与血栓形成的风险增加有关，自发性 流产（育龄妇女）、血小板减少症，以及 其他几种有时被提到的表现形式 统称为“抗磷脂抗体综合征”。以来 发现β 2-糖蛋白1（β 2G 1）是一种必需的成分， 大多数ACA和可能的拉克的反应性， 这些抗体与β 2G 1、与磷脂以及 与β 2Gl-磷脂复合物的关系已经变得非常重要。的 这项建议的目的是： 1)为了确定特定区域和关键氨基酸残基， 参与心磷脂（CL）和其它阴离子型磷脂酶C的结合 磷脂 2)为了鉴定β 2G 1、CL和β 2G 1-CL复合物中的表位， 与拉克/ACA结合。 3)研究表位特异性LAC/ACA的功能特性 亚群，并将表位特异性与 血栓形成 这些研究将利用β 2G 1的表达突变体、单克隆抗体、单克隆抗体和单克隆抗体。 针对β 2G 1的抗体、模拟表面的合成肽 β 2G 1分子的特性，以及在小鼠中的动物血栓形成模型。 其用于测试抗体亚群的血栓形成潜力。我们 我相信，对β 2Gl-CL复合物组装的理解 以及分离和确定的功能特性， 表位特异性的拉克/ACA亚群将导致更好的 了解引起血栓栓塞风险的机制， 与这些疾病相关的其他临床表现 抗体的

项目成果

The lupus anticoagulant/antiphospholipid syndrome.

狼疮抗凝/抗磷脂综合征。

• DOI: 10.1146/annurev.med.47.1.533
• 发表时间: 1996
• 期刊: Annual review of medicine
• 影响因子: 10.5
• 作者: Shapiro,SS

Prevalence of heparin-associated antibodies without thrombosis in patients undergoing cardiopulmonary bypass surgery.

接受体外循环手术的患者中无血栓形成的肝素相关抗体的患病率。

• DOI: 10.1161/01.cir.95.5.1242
• 发表时间: 1997
• 期刊: Circulation
• 影响因子: 37.8
• 作者: Bauer,TL;Arepally,G;Konkle,BA;Mestichelli,B;Shapiro,SS;Cines,DB;Poncz,M;McNulty,S;Amiral,J;Hauck,WW;Edie,RN;Mannion,JD
• 通讯作者: Mannion,JD