RITP患者血漿中利福平依賴性抗血小板抗體的特性及其作用機制
發(fā)布時間:2018-05-09 10:24
本文選題:利福平 + 血小板減少癥; 參考:《解放軍醫(yī)學雜志》2017年05期
【摘要】:目的研究利福平誘導的免疫性血小板減少癥(RITP)患者血漿中的利福平依賴性抗體(Rd-Ab)的特性及其誘導出血的可能機制,并探索治療RITP藥物的效果和作用特征。方法提取RITP患者血漿,通過流式細胞術、單克隆抗體俘獲血小板抗原(MAIPA)法及血小板聚集試驗檢測血清中Rd-Ab的特性。取NOD/SCID小鼠,建立RITP模型,觀察抗體對血小板的破壞機制,評價糖皮質激素和靜脈注射免疫球蛋白(IVIG)單獨或聯(lián)合使用對保護血小板的療效。結果體外實驗證實RITP患者血清中存在利福平依賴性抗體(Rd-Ab),該抗體與血小板的結合可被抗糖蛋白Ⅱb/Ⅲa單抗AP2完全阻斷,證明其與糖蛋白Ⅱb/Ⅲa的結合位點是鈣離子依賴性抗原決定簇。血小板聚集試驗顯示,Rd-Ab可抑制血小板聚集。小鼠體內實驗結果顯示,Rd-Ab可致小鼠體內人血小板被迅速清除,單用糖皮質激素可阻斷Rd-Ab誘導的人血小板清除,延長血小板平均壽命(MPL),該作用在24h后起效,72h療效達最佳,而IVIG可即刻起效。與RITP小鼠模型組相比(MPL 1.1±0.2h),糖皮質激素單獨治療組和IVIG單獨治療組的MPL分別延長至4.7±0.7h和4.2±1.1h(P0.05),兩藥聯(lián)合治療組血小板MPL達6.2±1.5h(P0.05)。結論 Rd-Ab與血小板膜糖蛋白Ⅱb/Ⅲa上的鈣離子依賴性抗原決定簇結合,從而抑制血小板聚集。Rd-Ab可導致小鼠血中人血小板的迅速清除,糖皮質激素和IVIG干預均可在一定程度上抑制血小板清除,IVIG起效更快,但兩藥聯(lián)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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