Résumé
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.