Therapeutic Effect And Mechanism Of All-trans-retinoic Acid Treatment In Refractory Idiopathic Thrombocytopenic Purpura

ObjectivePartⅠ:To explore the alterations of specific antibodies against platelet membranes glycoprotein (GPIb/IX,GPⅢa and GPⅡb) in patients which refractory idiopathic thrombocytopenic purpura (RITP) after ATRA therapy.PartⅡ:To explore therapeutic effect of all-trans-retinoic acid (ATRA) treatment in refractory idiopathic thrombocytopenic purpura (RITP) and to investgate the alterations of peripheral blood CD4+CD25highT cell and serum cytokines after ATRA treatment.MethodsPartⅠ: Monoclonal antibody-specific immobilization of platelet antigens (MAIPA) was performed. With improved method, the concentrations of specific antibodies against platelet membranes glycoprotein (GPIb/IX,GPⅢa and GPⅡb) were deteced in 28 RITP patients before and after treatment and in 17 normal individuals (control).PartⅡ:The expression of peripheral blood CD4+CD25highT cells was detected by flow cytometry and the concentrations of serum transforming growth factor-beta1 (TGF-β1), interleukin(IL)-10, IL-4, IL-2 and interferon(IFN)-γwere measured by ELISA in 28 RITP patients before and after treatment and in 17 normal individuals (control). ResultsPartⅠ:Before ATRA treatment in RITP patients, the overall positive rate of specific antibodies against platelet membranes glycoprotein (GPIb/IX,GPⅢa and GPⅡb) was 53.57%, which was significantly higher than control(P<0.01).However after ATRA treatment, the overall positive rate of specific antibodies against platelet membranes glycoprotein (GPIb/IX,GPⅢa and GPⅡb) was decreased to 42.86%, but showed no statistical difference in comparison with before treatment.PartⅡ:The overall response rate of ATRA treatment in RITP patients was 53.6%, the mean platelets counts were increased from 25.7±9.6×109/L to 109.1±30.1×109/L in the improved patients (P<0.01). The expression of CD4+CD25highT cells in the improved group after treatment was significantly higher than that before treatment(P<0.05), the concentrations of serum TGF-β1 and IL-4 in the improved group were increased(P<0.05), while the concentration of serum IFN-γwas decreased(P<0.05). However, the concentrations of serum IL-10 and IL-2 were not changed during ATRA trerapy period.ConclusionPartⅠ:ATRA can decrease a short part of antibodies against platelet membranes glycoprotein (GPIb/IX,GPⅢa and GPⅡb) of improved RITP patients,but no specificity.PartⅡ:The response rate by ATRA was 53.6% in RITP patients. ATRA may increase the expression of CD4+CD25highT cells in peripheral blood,which might be associated with elevation of TGF-β1 and IL-4,and decrease in IFN-γ.All these effects would restore the physiologic balance from immune disturbance.