ANTIPHOSPHOLIPID ANTIBODY (PREGNANCY IN SLE)

抗磷脂抗体（系统性红斑狼疮妊娠）

• 批准号: 3156450
• 负责人: AZZUDIN E GHARAVI
• 金额: $ 4.78万
• 依托单位: HOSPITAL FOR SPECIAL SURGERY
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-04-01 至 1993-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3156450
• 关键词: antibody; anticoagulants; antiidiotype antibody; apolipoproteins; autoantibody; disease /disorder model; electrofocusing; embryo /fetus death; enzyme linked immunosorbent assay; female; human tissue; laboratory mouse; laboratory rabbit; pathologic process; phospholipids; placenta; pregnancy disorder; pregnancy immunology; systemic lupus erythematosus; thrombocytopenia; thrombosis

Antiphospholipid antibody (aPL) is closely associated with recurrent fetal death, thrombosis, and thrombocytopenia. The mechanisms by which the antibody causes the complications remain unexplained. The specific goals of this proposal are: 1. To characterize the idiotypes of human polyclonal and mouse monoclonal aPL antibodies and to define "pathogenic" public idiotypes. Anti-id will also be used to detect aPL in the placenta and other tissues by immunofluorescence. 2. To define the pathophysiology aPL. The effect of aPL on the activity of the placental anticoagulant protein (PAP) will be analyzed by ELISA as well as PL-dependent coagulation assays, KCT and APTT. The interaction of aPL with the lupus cofactor (apolipoprotein H) will be evaluated by ELISA and KCT and APTT coagulation assays. The levels of cofactor in patients' sera will be determined by ELISA and the co factor isoforms identified by isoelectric focusing. Associations between PAP levels, cofactor levels, cofactor isoforms and clinical complications will be assessed. 3. To explore the pathogenic nature of the antibody in spontaneous (MRL/lpr) and induced mouse models. Human polyclonal and mouse monoclonal antibodies will be administered to normal pregnant mice, or antiphospholipid antibodies will be induced in normal mice by immunization with apolipoprotein H. The effect on pregnancy (number of pups) and hematology (platelets, thrombosis) will be determined. To suppress aPL production, anti-id antibodies will be administered to MRL/lpr mice and circulating aPL levels, platelets and pregnancy outcome monitored. 4. To determine the VH sequences of aPL genes so as to define the genetic origins of aPL in MRL mice. The characterization and functional evaluation of PAP, lupus cofactor, and anti-id antibodies will determine whether aPL antibodies are directly involved in the pathogenesis of the syndrome and may uncover their pathogenesis. Identification of pathogenic idiotypes and the genetic origin of aPL may provide tools to identify patients at risk.

抗磷脂抗体（APL）与复发密切相关 胎儿死亡，血栓形成和血小板减少症。 所在的机制 抗体导致并发症仍然无法解释。 具体 该提议的目标是： 1。表征人类多克隆和小鼠的白痴 单克隆APL抗体并定义“致病”公共惯用型。 抗ID也将用于检测胎盘和其他的APL 通过免疫荧光组织。 2。定义病理生理学。 APL对 将分析胎盘抗凝蛋白（PAP）的活性 由ELISA以及PL依赖性的凝结测定，KCT和APTT。 这 APL与狼疮辅因子（载脂蛋白H）的相互作用将是 由ELISA和KCT和APTT凝血测定法进行评估。 水平 患者血清中的辅助因子将由ELISA和CO因子确定 通过等电聚焦确定的同工型。 PAP之间的关联 水平，辅因子水平，辅因子同工型和临床并发症 将被评估。 3。探索自发抗体的致病性 （MRL/LPR）和诱导的小鼠模型。 人类多克隆和小鼠 单克隆抗体将用于正常的怀孕小鼠，或 抗磷脂抗体将在正常小鼠中诱导 用载脂蛋白H进行免疫。 将确定幼崽）和血液学（血小板，血栓形成）。 到 抑制APL产生，抗ID抗体将被施用 MRL/LPR小鼠和循环APL水平，血小板和妊娠结局 受监控。 4。确定APL基因的VH序列以定义 MRL小鼠APL的遗传起源。 PAP的表征和功能评估，狼疮辅因子， 抗ID抗体将确定APL抗体是否为 直接参与综合征的发病机理，可能会发现 它们的发病机理。 鉴定致病性型和 APL的遗传起源可以提供识别有风险患者的工具。