Tim-3及其配体Galectin-9在多发性骨髓瘤患者Th1/Th2细胞失衡中的意义  

Significance of Tim-3 and Its Ligand Galectin-9 in Th1/Th2 Imbalance in Patients with Multiple Myeloma

作　　者：张瑞[1] 陈双[1] 骆婷婷 曲建华[1] ZHANG Rui;CHEN Shuang;LUO Ting-Ting;QU Jian-Hua(Center of Hematologic Diseases,The First Affiliated Hospital of Xinjiang Medical University,Hematology Institute of Xinjiang Uygur Autonomous Region,Urumqi 830054,Xinjiang Uygur Autonomous Region,China)

机构地区：[1]新疆医科大学第一附属医院血液病中心,新疆维吾尔自治区血液病研究所,新疆乌鲁木齐830054

出　　处：《中国实验血液学杂志》2023年第6期1764-1770,共7页Journal of Experimental Hematology

基　　金：国家自然科学基金(82160034)。

摘　　要：目的:探讨Tim-3及Galectin-9在多发性骨髓瘤患者Th1/Th2细胞失衡中的意义。方法:纳入初诊MM患者55例,健康对照20例,流式细胞术检测外周血CD4^(+)T细胞上Tim-3的表达水平、Th1和Th2细胞水平、Tim-3^(+)Th1和Tim-3^(+)Th2细胞水平,ELISA法检测血清中IFN-γ和IL-4的水平,PCR检测Galectin-9mRNA的水平,并分析Galectin-9mRNA表达与Th细胞亚群和细胞因子水平的相关性,以及Tim-3^(+)Th1/Tim-3^(+)Th2与相应临床特征的关系。结果:MM患者Tim-3^(+)CD4^(+)T细胞、Tim-3^(+)Th1、Tim-3^(+)Th2细胞水平及Tim-3^(+)Th1/Tim-3^(+)Th2细胞比值较健康对照组明显升高(P<0.05),Th1细胞水平及Th1/Th2细胞比值明显下降(P<0.05)。MM患者血清中IFN-γ及IFN-γ/IL-4比值明显下降(P<0.05),IL-4水平明显升高(P>0.05),Galectin-9mRNA的水平明显高于健康对照组(P<0.05)。Galectin-9mRNA与Tim-3^(+)CD4^(+)T细胞、Tim-3^(+)Th2细胞、IL-4均呈正相关(r=0.663,r=0.492,r=0.470),与IFN-γ呈负相关(r=-0.593)。进一步分析显示,患者Tim-3^(+)Th1/Tim-3^(+)Th2细胞比值与临床ISS分期、有溶骨性损害、染色体核型异常呈正相关(r=0.511,r=0.556,r=0.632)。结论:Tim-3及Galectin-9参与了MM患者Th1/Th2失衡,并且Tim-3^(+)Th1/Tim-3^(+)Th2细胞比值高与临床预后较差的指标有关。Objective:To investigate the significance of Tim-3and Galectin-9in Th1/Th2imbalance in patients with multiple myeloma(MM).Methods:55newly diagnosed MM patients and20healthy controls were included.Flow cytometry was used to detect the expression of Tim-3on CD4+ T cells,the proportion of Th1,Th2,Tim-3+ Th1and Tim-3+ Th2cells in peripheral blood.ELISA was used to detect the levels of cytokines IFN-γand IL-4in serum,and PCR was used to detect the level of Galectin-9 mRNA.Then the correlations between Galectin-9 mRNA expression and Th-cell subsets and related cytokine levels,as well as the relationship between Tim-3+ Th1/Tim-3+ Th2ratio and corresponding clinical features were analyzed.Results:Compared with the control group,the expression of Tim-3on CD4+ T cells in peripheral blood of MM patients was significantly increased(P<0.05),the proportions of Tim-3+ Th1cells,Tim-3+ Th2cells and Tim-3+ Th1/Tim-3+ Th2ratio in MM patients were also increased(P<0.05),while the proportion of Th1cells and Th1/Th2ratio in MM patients were significantly decreased(P<0.05).The level of cytokine IFN-γand IFN-γ/IL-4ratio in MM patients were significantly decreased(P<0.05),while the level of cytokine IL-4was increased(P<0.05).The mRNA levels of Galectin-9 in MM patients were significantly increased(P<0.05).The levels of Galectin-9 mRNA were positively correlated with Tim-3+ CD4+ T cells(r= 0.663),Tim-3+Th2cells(r= 0.492)and IL-4(r= 0.470),while negatively correlated with IFN-γ(r=-0.593).The ratios of Tim-3+ Th1/Tim-3+ Th2in MM patients were positively correlated with ISS stage(r= 0.511),osteolytic damage(r=0.556)and chromosome abnormality(r= 0.632).Conclusion:These results suggest that Tim-3and Galectin-9are involved in Th1/Th2imbalance in MM patients,and the high ratio of Tim-3+ Th1/Tim-3+ Th2is associated with poor clinical prognosis.

关 键 词：多发性骨髓瘤 TIM-3 GALECTIN-9 TH1 TH2 

分 类 号：R733.3[医药卫生—肿瘤]