沙利度胺对多发性骨髓瘤患者外周血Th17细胞影响的研究

Effects of Thalidomide on Peripheral Blood Th17 Cells of Patients with Multiple Myeloma

目的:探讨沙利度胺治疗多发性骨髓瘤(multiple myeloma,MM)患者前后外周血辅助T细胞17(Th17)变化及其意义。方法:研究对象为35例沙利度胺治疗的MM患者及35例同期健康体检者,采用流式细胞术检测外周血Th17细胞百分率,实时定量PCR检测核转录因子维甲酸相关孤儿受体γt(retinoid-related orphan receptor gamma-t,RORγt)mRNA表达水平,酶联免疫吸附法检测血浆白细胞介素17(interleukin-17,IL-17)水平。结果:MM患者外周血中Th17细胞百分率、RORγt mRNA表达水平及血浆IL-17水平均明显高于正常对照组,差异均有统计学意义(P<0.05)。MM患者外周血中Th17细胞百分率与性别、年龄、疾病分型、球蛋白、免疫球蛋白、轻链、M蛋白及骨髓浆细胞比例无明显相关性(P>0.05),而与疾病ISS分期、β2-微球蛋白水平及血浆中IL-17水平有关(P<0.05)。沙利度胺治疗有效的MM患者外周血中Th17细胞百分率、RORγt mRNA表达水平及血浆IL-17水平均比治疗前明显降低,其差异均有统计学意义(P<0.05)。结论:MM患者外周血Th17细胞数增多,抑制Th17细胞可能是沙利度胺发挥抗MM作用的机制之一。

Objective: To explore the change of T help cell 17( Th17) in the peripheral blood of patients with multiple myeloma( MM) before and after treatment with thalidomide. Methods: A total of 35 MM patients treated with thalidomide and 35 healthy controls were enrolled in this study. The percentage of Th17 cells were detected by flow cytometry.The mRNA levels of retinoid-related orphan receptor gamma-t( RORγt) were detected by real-time quantitative reverse transcription polymerase chain reaction( RT-PCR) and the plasm IL-17 levels were measured by enzyme linked immunosorbent assay( ELISA). Results: The percentage of Th17 cells,the mRNA expression of RORγt and the plasm IL-17 levels in patients with MM were statistically higher than those in normal controls( P < 0. 05). The percentage of Th17 cells was not correlate with the sex,age,disease type,globulin,immune globulin,light chain,M-protein and the proportion of plasmocytes( P > 0. 05),but correlated with ISS stage,the level of β2-microglobulin and the plasm IL-17levels( P < 0. 05). The percentage of Th17 cells,the mRNA expression of RORγt and the plasm IL-17 levels in patients with response to thalidomide were statistically lower than those in patients before treatment( P < 0. 05). Conclusion:The Th17 cells increase in the peripheral blood of patients with MM,the Th17 cells may participate in the occurrence of MM. Thalidomide may exert anti-MM through down-regulating Th17 cells.