解放军医学杂志2017，Vol.42Issue(5)：413-419,7.DOI:10.11855/j.issn.0577-7402.2017.05.10
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
Study on the characteristics and mechanisms of rifampicin dependent antiplatelet antibody in plasma of patients with RITP
摘要
Abstract
Objective Drug-induced immune thrombocytopenia (DITP) is a major adverse drug effect mediated by drugdependent antibodies.It can be actuated by a wide range of medications,including Rifampicin.Methods Rifampicin-dependent antibody (rd-Ab) from a rifampicin-treated tuberculosis patient with thrombocytopenia (RITP) was characterized by in vitro and in vivo assays,which includes flow cytometry,monoclonal antibody immobilization of platelet antigens (MAIPA) assay,platelet aggregation assay and RITP mouse model.Results The rd-Ab could bind glycoprotein (GP) Ⅱ b/Ⅲ a,as shown by the MAIPA assay.The binding of rd-Ab could be blocked by AP2,a monoclonal antibody that binds a calcium dependent site on GP Ⅱ b/Ⅲ a complex and inhibits ADP-induced platelet aggregation.These results suggested that rd-Ab binds the same site or proximal sites on the GP Ⅱ b/Ⅲ a complex as AP2.Furthermore,the rd-Ab inhibited platelet aggregation in vitro.In an established NOD/SCID mouse model of RITP,the rd-Ab caused a rapid clearance of human platelets (MPL=1.1 ± 0.2h).The in vivo platelet loss could be partially prevented by treatments with intravenous immunoglobulin (IVIG) or corticosteroids (MPL=4.7 ± 0.7h and 4.2 ± 1.1h,P＜0.05).Slowing of platelet clearance was observed immediately upon IVIG treatment,while upon corticosteroid treatment at 24h,and reaching its peak at 72h.Combination of IVIG and corticosteroid treatments was more efficacious (MPL=6.2 ± 1.5h,P＜0.05).Conclusions 1.The rd-Ab binds to calcium-dependent-epitopes on the calcium dependent site of GP Ⅱ b/Ⅲ a complex,which causes platelet damage and inhibits platelet aggregation.2.Either IVIG or corticosteroid alone can partially block platelet clearance by rd-Ab.Slowing of platelet clearance is observed immediately upon IVIG treatment,or upon corticosteroid treatment several days later,indicating that IVIG may be more suitable for acutely raising the platelet count than corticosteroid treatment for RITP.3.Combination of IVIG and corticosteroid treatment is more efficacious than IVIG or corticosteroids alone.关键词
利福平/血小板减少症/糖蛋白Ⅱb/Ⅲa/模型,动物Key words
rifampicin/thrombocytopenia/glycoprotein Ⅱ b/Ⅲ a/models,animal分类
医药卫生引用本文复制引用
孙平,吴广胜,梁迅..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[J].解放军医学杂志,2017,42(5):413-419,7.基金项目
国家自然科学基金面上项目(81370619) （81370619）
锦州医科大学校长基金-奥鸿博泽科技创新基金(AH2014010)This work was supported by the National Natural Science Foundation of China (81370619),and Aohongboze Graduate Sci-tech Innovation Foundation and President Fund of Jinzhou Medical University (AH2014010) （AH2014010）
