RITP患者血浆中利福平依赖性抗血小板抗体的特性及其作用机制

发布时间：2018-05-09 10:24

  本文选题：利福平 + 血小板减少症　； 参考：《解放军医学杂志》2017年05期

【摘要】：目的研究利福平诱导的免疫性血小板减少症(RITP)患者血浆中的利福平依赖性抗体(Rd-Ab)的特性及其诱导出血的可能机制,并探索治疗RITP药物的效果和作用特征。方法提取RITP患者血浆,通过流式细胞术、单克隆抗体俘获血小板抗原(MAIPA)法及血小板聚集试验检测血清中Rd-Ab的特性。取NOD/SCID小鼠,建立RITP模型,观察抗体对血小板的破坏机制,评价糖皮质激素和静脉注射免疫球蛋白(IVIG)单独或联合使用对保护血小板的疗效。结果体外实验证实RITP患者血清中存在利福平依赖性抗体(Rd-Ab),该抗体与血小板的结合可被抗糖蛋白Ⅱb/Ⅲa单抗AP2完全阻断,证明其与糖蛋白Ⅱb/Ⅲa的结合位点是钙离子依赖性抗原决定簇。血小板聚集试验显示,Rd-Ab可抑制血小板聚集。小鼠体内实验结果显示,Rd-Ab可致小鼠体内人血小板被迅速清除,单用糖皮质激素可阻断Rd-Ab诱导的人血小板清除,延长血小板平均寿命(MPL),该作用在24h后起效,72h疗效达最佳,而IVIG可即刻起效。与RITP小鼠模型组相比(MPL 1.1±0.2h),糖皮质激素单独治疗组和IVIG单独治疗组的MPL分别延长至4.7±0.7h和4.2±1.1h(P0.05),两药联合治疗组血小板MPL达6.2±1.5h(P0.05)。结论 Rd-Ab与血小板膜糖蛋白Ⅱb/Ⅲa上的钙离子依赖性抗原决定簇结合,从而抑制血小板聚集。Rd-Ab可导致小鼠血中人血小板的迅速清除,糖皮质激素和IVIG干预均可在一定程度上抑制血小板清除,IVIG起效更快,但两药联合效果更好。
[Abstract]:Objective to study the characteristics of rifampicin-dependent antibody (Rd-Ab) in the plasma of patients with rifampicin-induced immune thrombocytopenia (RITP) and the possible mechanism of inducing bleeding, and to explore the effect and action of rifampicin-induced RITP. Methods the plasma of RITP patients was extracted, and the characteristics of Rd-Ab in serum were detected by flow cytometry, monoclonal antibody capture platelet antigen (MAIPA) method and platelet aggregation test. The RITP model was established in NOD/SCID mice to observe the mechanism of platelet destruction induced by antibodies and to evaluate the effect of glucocorticoid and intravenous immunoglobulin (Ig) alone or in combination on platelet protection. Results in vitro, rifampicin-dependent antibody was found in the serum of RITP patients. The binding of rifampicin-dependent antibody to platelets could be completely blocked by anti-glycoprotein 鈪，

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