45例多发性骨髓瘤患者细胞免疫功能变化及其临床意义

Cellular immune function and its clinical implications in 45 patients with multiple myeloma

目的 探讨多发性骨髓瘤（MM）患者细胞免疫功能变化及其临床意义.方法 45例MM患者分为初诊组（18例）、治疗后病情稳定期组（17例）和复发/难治组（10例）,以20名健康志愿者为正常对照组.采用流式细胞术检测外周血T细胞亚群、NK细胞、树突细胞（DC）、辅助性T细胞（Th1和Th2）、调节性T细胞（Treg）和Th17细胞在CD4＋细胞中所占比率.结合患者血清β2微球蛋白（β2-MG）、LDH和HGB水平进行分析.结果 ①初诊组患者Treg、NK细胞比率及CD4＋/CD8＋细胞、DC1/DC2、Th1/Th2比值较正常对照组和病情稳定期组均降低,IL-17A/Treg比值显著升高（P值均＜0.05）;与病情稳定期组相比,复发/难治组患者CD4＋/CD8＋细胞、Th1/Th2比值显著下降,IL-17A/Treg比值显著升高（P值均＜0.05）.②随着临床ISS分期增高,CD4＋/CD8＋细胞、Th 1/Th2比值明显降低,IL-17A/Treg比值明显升高（P值均＜0.05）.③MM患者CD4＋/CD8＋细胞、Th 1/Th2、DC 1/DC2比值与血清β2-MG和LDH的表达水平呈显著负相关（P值均＜0.05）;IL-17A/Treg比值与两者呈显著正相关（P值均＜0.05）;各项免疫指标与HGB水平无明显相关性（P值均＞0.05）.结论 CD4＋/CD8＋细胞、Th 1/Th2、DC1/DC2以及IL-17A/Treg比值的异常与MM患者的病情分期、疗效、发展以及预后密切相关.

Objective To investigate cellular immune function and its clinical significance in patients with multiple myeloma （MM）.Methods 45 MM patients were divided into three groups：newly diagnosed （n=18）,stable stage （n=17） and relapsed/refractory （n=10）.The frequencies of T cell subtypes,natural killer （NK） cells,dendritic cells （DC）,helper T cells （including Th1 and Th2）,regulatory T cells （Treg） and Th17 cells in peripheral blood were detected by flow cytometry.Serum concentrations of β2 microglobulin （β2-MG）,lactate dehydrogenase （LDH） and hemoglobin （Hb） were also detected,respectively.Results Compared with controls and stable stage group,the ratios of CD4＋/CD8＋,DC1/DC2,and Th1/Th2,the numbers of Treg and NK cells were significantly lower in newly diagnosed group.However,the ratio of IL-17A/Treg was significantly higher in newly diagnosed group （P〈0.05）.Compared with stable stage group,the ratios of CD4＋/CD8＋,DC 1/DC2 and Th 1/Th2 were significantly lower,and the ratio of IL-17A/Treg was significantly higher in relapsed/refractory group （P〈0.05）.In higher ISS stages,the ratios of CD4＋/CD8＋ and Th1/Th2 were significantly lower and the ratio of IL-17A/Treg was significantly higher （P〈0.05）.There were negative correlations between the ratios of CD4 ＋/CD8 ＋,DC1/DC2,Th1/Th2 and the levels of β2-MG and LDH,respectively （P〈0.05）.The ratio of IL-17A/Treg was positively correlated with the levels of β2-MG and LDH （P〈0.05）.They were no correlated with the level of Hb （P〉0.05）.Conclusion The abnormal ratios of CD4＋/CD8＋,DC1/DC2,Th1/Th2 and IL-17A/Treg were closely related with disease condition stages,treatment outcomes,progression and prognosis in MM patients.