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

半乳糖凝集素 多发性骨髓瘤 流式细胞术 细胞因子 免疫学 信使核糖核酸 医学 内科学 内分泌学 生物 基因 生物化学
作者
Rui Zhang,Shuang Chen,Tingting Luo,Jianhua Qu
出处
期刊:PubMed 卷期号:31 (6): 1764-1770
标识
DOI:10.19746/j.cnki.issn.1009-2137.2023.06.025
摘要

To investigate the significance of Tim-3 and Galectin-9 in Th1/Th2 imbalance in patients with multiple myeloma (MM).55 newly diagnosed MM patients and 20 healthy controls were included. Flow cytometry was used to detect the expression of Tim-3 on CD4+T cells, the proportion of Th1, Th2, Tim-3+Th1 and Tim-3+Th2 cells in peripheral blood. ELISA was used to detect the levels of cytokines IFN-γ and IL-4 in 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+Th2 ratio and corresponding clinical features were analyzed.Compared with the control group, the expression of Tim-3 on CD4+T cells in peripheral blood of MM patients was significantly increased (P<0.05), the proportions of Tim-3+Th1 cells, Tim-3+Th2 cells and Tim-3+Th1/Tim-3+Th2 ratio in MM patients were also increased (P<0.05), while the proportion of Th1 cells and Th1/Th2 ratio in MM patients were significantly decreased (P<0.05). The level of cytokine IFN-γ and IFN-γ/IL-4 ratio in MM patients were significantly decreased (P<0.05), while the level of cytokine IL-4 was 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+Th2 cells (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+Th2 in MM patients were positively correlated with ISS stage (r=0.511), osteolytic damage (r=0.556) and chromosome abnormality (r=0.632).These results suggest that Tim-3 and Galectin-9 are involved in Th1/Th2 imbalance in MM patients, and the high ratio of Tim-3+Th1/Tim-3+Th2 is associated with poor clinical prognosis.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.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.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-9 mRNA的水平,并分析Galectin-9 mRNA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.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-9 mRNA的水平明显高于健康对照组(P<0.05)。Galectin-9 mRNA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).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.

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