T细胞亚群与细胞因子水平变化在多发性骨髓瘤患者临床诊疗及预后评估中的价值

The Value of T Cell subsets and Cytokine Levels Changes in the Clinical Diagnosis, Treatment and Prognosis Evaluation of Multiple Myeloma

目的:探讨多发性骨髓瘤(MM)患者T淋巴细胞亚群及细胞因子的变化与免疫功能状态、生化指标的相关性以及与临床病情阶段及预后的关系,为MM患者预后分析及病情监测提供科学依据。方法:收集两家医院共89例MM患者的临床资料,同时选取36例健康者为对照组,采用流式细胞术、酶联免疫吸附试验(ELISA)分别检测入组患者外周血T淋巴细胞亚群核心成员及细胞因子的水平,同时应用全自动生化分析仪与全自动血细胞分析仪检测血清β_(2)-微球蛋白(β_(2)-MG)、乳酸脱氢酶(LDH)、白蛋白(ALB)、肌酐(CRE)以及血红蛋白(HGB)水平,并探究T淋巴细胞亚群与上述各指标之间的关系及其临床意义。结果:MM患者外周血中NK细胞、CD8^(+)T淋巴细胞数显著高于对照组(P<0.01),CD4^(+)T、CD4^(+)/CD8^(+)比值低于对照组(P<0.05);而MM患者外周血中CD3^(+)T细胞数与对照组比较无显著统计学差异(P>0.05)。MM患者CD4^(+)T、CD4^(+)/CD8^(+)比值低于正常对照,且与MM分期呈负相关(r=-0.964,r=-0.653),即MM分期越晚其水平减低越明显;而CD8^(+)T、NK细胞比例则与MM分期呈正相关(r=0.891,r=0.728),即MM分期越晚其水平升高越显著。MM患者Treg细胞(CD4^(+)CD25^(high)CD127^(low/-)T细胞/CD4^(+)T细胞)水平在疾病分期Ⅰ期、Ⅱ期、Ⅲ期分别为(5.87±0.92)%、(7.97±1.32)%、(11.52±4.71)%,与对照组比较差异有统计学意义(P<0.05),且Ⅲ期MM患者Treg细胞水平显著高于对照组及其他病情阶段的患者(P<0.01)。MM患者Treg细胞(CD4^(+)CD25^(high)CD127^(low/-)T细胞/CD4^(+)T细胞)的比例与β2-MG浓度、LDH水平呈正相关性(r=0.793,r=0.536),但与HGB、ALB以及CRE无显著性相关性。MM患者血清IL-6、IL-10、TNF-α水平显著高于对照组(P<0.05),与MM分期密切相关(r=0.839,r=0.917,r=0.746),即MM分期越晚,其水平越高;而血清IFN-γ水平与MM疾病分期呈负相关(r=-0.689),随疾病分期增加其水平逐渐减低(P<0.01);IL-2、IL-4水平与病情阶段无显著相关性,但总体较对照组均上调(P<0.05)。结论:T淋巴细胞亚群核心成员及各细胞因子水平异常与MM患者病情进展、预后不良密切相关,是MM患者病情监测的有效指标。

Objective: To explore the correlation between the changes of T lymphocyte subsets and cytokines in patients with M M and immune function status,biochemical indicators,and their relationships with clinical stage and prognosis,which is expected to provide a scientific basis for the prognosis analysis and condition monitoring of M M patients.Methods: The clinical data of 89 M M patients in two hospitals were collected,and 36 healthy people without tumor or infectious diseases were selected as the control group.Flowcytometry and enzyme-linked immunosorbent assay(ELISA) were used to detect the changes of core members of peripheral blood T lymphocyte subsets and cytokine levels,respectively.At the same time,automatic biochemical analyzer and automatic blood cell analyzer were used to detect serum β_(2)-microglobulin(β_(2)-M G),lactate dehydrogenase(LDH),albumin(ALB),creatinine(CRE) and hemoglobin(HGB) levels,and the relationship between T lymphocyte subsets and the above indexes and their clinical significance were analyzed.Results: The proportions of NK cells and CD8^(+)T lymphocytes in the peripheral blood of M M patients were significantly higher than that of the control group(P<0.01),the proportion of CD4^(+)T and the ratio of CD4^(+)/CD8^(+)were lower than those of the control group(P<0.05);however,there was no significant difference in the numbers CD3^(+)T cells compared with the control group(P>0.05).The proportion of CD4^(+)T and ratios of CD4^(+)/CD8^(+)in M M patients were lower than those of normal controls,and were negatively correlated with M M staging(r =-0.964,r =-0.653),that is,the later the M M staging,the more obvious their levels were reduced,while CD8^(+)T and NK cells were positively correlated with M M staging(r=0.891,r=0.728),that is,the later the M M staging,the more significant their levels increased.The levels of Treg cells(CD4^(+)CD25^(high)CD127^(low/-)T cells/CD4^(+)T cells) of M M patients in the disease stage Ⅰ,Ⅱ and Ⅲ were(5.87 ± 0.92) %,(7.97 ± 1.32) %,(11.52 ± 4.71) %respectively,the difference was statistically significant compared with control group(P<0.05),and the level of Treg cells in M M patients with stage III was significantly higher than that in controls and patients with other disease stages(P<0.01).The proportion of Treg cells(CD4^(+)CD25^(high)CD127^(low/-)T cells/CD4^(+)T cells) in M M patients was positively correlated with the concentration of β_(2)-M G and LDH(r=0.793,r=0.536),but had no significant correlation with HGB,ALB and CRE.The serum levels of IL-6,IL-10 and TNF-α in M M patients were significantly higher than those in the control group(P<0.05),which were closely related to M M staging(r=0.839,r=0.917,r=0.746),that is,the later the M M staging,the higher the levels;The serum IFN-γ level was negatively correlated with the stage of M M(r=-0.689),and its level gradually decreased with the increase of the disease stage and degree(P<0.01).There was no significant correlation between the levels of IL-2 and IL-4 and the disease stage,but they were all up-regulated compared with the control group(P<0.05).Conclusion: The abnormal regulation of the core members of T lymphocyte subsets and the levels of various cytokines are closely related to the disease progression and poor prognosis of M M patients,which is an effective indicator for the disease monitoring of M M patients.