不同治疗方案对原发免疫性血小板减少症患者外周血调节T细胞水平变化的影响及其意义分析(英文)

目的:探讨原发免疫性血小板减少症(immune thrombocytopenia,ITP)患者治疗前后外周血调节性T细胞(regulatory T cell,Treg)水平变化及其在ITP发病中的作用。方法:选取2010年6月至2013年7月间276例新诊断ITP患者,男114例、女162例,中位年龄40(18-70)岁。按治疗方案随机分为地塞米松组(90例):地塞米松40 mg/d第1~4天口服;泼尼松组(98例):泼尼松1.5 mg·kg-1·d-1口服;2泼尼松组(98例):泼尼松1.5 mg·kg-1·d-1口服;地塞米松+小剂量利妥昔单抗组(88例):地塞米松40 mg/d第1-4天口服,利妥昔单抗100 mg第7、14、21、28天静脉滴注。各组患者于治疗前、治疗后14 d和28 d分别采取外周静脉血,采用流式细胞术检测CD4+CD25+CD127-细胞水平。以60名健康体检者为正常对照组。结果:治疗后第28天,地塞米松组、泼尼松组、地塞米松+小剂量利妥昔单抗组的总有效率分别66.7%、69.4%、79.5%,差异无统计学意义;随访12个月,泼尼松组(37.8%)和地塞米松组(22.7%)之间差异无统计学意义,而与地塞米松+小剂量利妥昔单抗组持续有效率(66.7%),差异有统计学意义(P0.05)。所有ITP患者治疗前外周血CD4+CD25+CD127-细胞表达水平低于健康对照组(1.66±0.69)%对(4.01±0.38)%,P0.05];地塞米松组、泼尼松组患者治疗后14d CD4+CD25high CD127low细胞水平均高于治疗前(3.46±0.76)%对(1.68±0.72)%、(3.22±0.77)%对(1.69±0.74)%,P值均0.05];地塞米松+小剂量利妥昔单抗组治疗后14、28d CD4+CD25+CD127-细胞水平(4.27±1.08)%、(4.43±0.62)%]均高于治疗前(1.67±0.67)%],差异有统计学意义(P值均0.05);治疗后28 d,泼尼松组、地塞米松组患者CD4+CD25+CD127-细胞水平(2.68±0.63)%、(2.58±0.66)%]与治疗前比较差异无统计学意义。结论:地塞米松联合小剂量利妥昔单抗在长期疗效及提升T细胞数量方面显著优于地塞米松和泼尼松,值得临床推广。

Clinical Effects of Different Therapeutic Methods on the Treatment of the Primary Immune Thrombocytopenia

Objective:To investigate the effect of Treg-cells on the primary immune thrombocytopenia by detecting the level changes of peripheral blood regulatory T cells of the patients with ITP before and after the treatments.Methods:276 patients with ITP who were treated in the department of hematology in our hospital from June 2010 to July 2013 were enrolled in the study. According to the different therapeutic methods, the selected patients were divided into three groups. DXMgroup (90 cases): dexamethasone 40 mg/d taken by mouth in 4 days; Prednisolone group(98 cases): prednisolone 1.5 mg·kg-1·d-1 taken by mouth; DXM+low dose Rituximab group (88 cases): dexamethasone 40 mg/d taken by mouth formthe 1st day to the 4th, and then the Rituximab 100 mg was given by intravenous drip on the 7th, 14th, 21th and 28th. Another 60 healthy people who were inspected in our hospital were chosen to be the control group. The peripheral vein blood of patients in each group at the 14th and 28th day before and after the treatments was taken separately in order to detect the levels of CD4+, CD25+, CD127- in Tr cells were examined by flow cytometry.Results:On the 28th day, the total effective rate of Prednisolone group, Dexamethasone (DXM) group and DXM+low dose Rituximab group was 69.4%, 66.7%and 79.5%, respectively, with no significant difference. In the 12-months'' follow-up, the continuous effective rate of DXM+low dose Rituximab group (66.7%) was higher than Prednisolone group(37.8%) and Dexamethasone (DXM) group (22.7%) with a significant difference(P<0.05). There was no significant difference between Prednisolone group and Dexamethasone (DXM) group. The expression levels on peripheral blood CD4+, CD25+ and CD127- T cells of the all ITP patients were lower than those of the patients in the health control group before the treatments(1.66± 0.69)%VS(4.01± 0.38)%, P<0.05]. On the 14th day, the levels of CD4+, CD25+ and CD127- Tr cells of patients in Prednisolone group and Dexamethasone (DXM) group were higher than before with an average rate of (3.46± 0.76)% VS (1.68± 0.72)%, (3.22± 0.77)% VS (1.69± 0.74)%, respectively, P<0.05]; On the 14th and 28th day of the treatments, the levels of CD4+, CD25+ and CD127- of the DXM+low dose Rituximab group were higher than before with significant differences (P<0.05). On the 28th day, the levels of CD4+, CD25+ and CD127- Tr cells of patients in Prednisolone group and Dexamethasone (DXM) group were (2.68± 0.63)%and (2.58± 0.66)%which showed no significant difference when comparing with before.Conclusion:The regimen of DXM+low dose Rituximab is superior to single medication of prednisolone and dexamethasone in promoting the number of T cells and long-term treatments.