亲缘HLA单倍体相合外周血造血干细胞移植后Tim-3/Galectin-9通路变化特点及临床意义  

Change characteristics of Tim-3/Galectin-9 pathway after related haploidentical peripheral blood stem cell transplantation and the clinical significance

作　　者：张友弟 于明凯 庞楠楠[1,3] 韩春霞 王洪波[1] 骆婷婷[1] 袁海龙 徐建丽[1] 陈刚[1] 江明[1] ZHANG Youdi;YU Mingkai;PANG Nannan;HAN Chunxia;WANG Hongbo;LUO Tingting;YUAN Hailong;XU Jianli;CHEN Gang;JIANG Ming(Hematology Center&Hematology Institute of Xinjiang Uygur Autonomous Region,First Affiliated Hospital of Xinji-ang Medical University,Urumqi 830054,China;Department of Immunology,School of Basic Medical Sciences,Xin-jiang Medical University,Urumqi 830011,China;Key Laboratory of Biomedical Technology,Suzhou Institute of Biomedical Engineering and Technology,Chinese Academy of Sciences,Suzhou 215163,China)

机构地区：[1]新疆医科大学第一附属医院血液病中心,乌鲁木齐830054 [2]新疆医科大学基础医药院免疫学教研室,乌鲁木齐830011 [3]中国科学院苏州生物医学工程技术研究所中国科学院生物医学检验技术重点实验室,苏州215163

出　　处：《免疫学杂志》2022年第6期544-552,共9页Immunological Journal

基　　金：国家自然科学基金(81960039);江苏省卓越博士后计划(JB0206035)。

摘　　要：目的探究Tim-3/Galectin-9负性信号通路在亲缘HLA单倍体相合外周血造血干细胞移植中的变化特点及其临床意义。方法以行单倍体造血干细胞移植的36例患者和20例健康者为研究对象,通过FCM监测患者及健康对照组外周血中CD4^(+)T细胞和Tim-3分子的表达情况,ELISA法检测移植后患者细胞因子Galectin-9、IFN-γ、IL-4、TGF-β和IL-17的动态变化。结果根据西雅图国际诊断标准,移植术后有14例患者发生aGVHD,22例患者未发生aGVHD。①未发生aGVHD患者移植后30~90 d CD4^(+)T细胞百分比均低于健康对照组(P<0.05);未发生aGVHD患者移植后血清中细胞因子Galectin-9、TGF-β、IFN-γ、IL-4和IL-17水平呈现逐渐增高的趋势,Galectin-9和TGF-β水平在移植后60 d达到正常值(P>0.05),IFN-γ、IL-4和IL-17在移植后第90天恢复到正常水平(P>0.05)。Spearman相关分析结果显示Galectin-9与TGF-β变化水平呈正相关(r=0.651,P=0.001);②发生aGVHD患者外周血中Tim-3^(+)CD4^(+)T细胞的百分比和IFN-γ、IL-17水平明显高于不发生aGVHD患者(P<0.01);不发生aGVHD患者的Galectin-9和TGF-β水平更高(P<0.05)。Spearman相关分析结果显示Tim-3^(+)CD4^(+)T细胞的百分比与IFN-γ水平呈正相关(r=0.631,P=0.015)。结论单倍体相合外周血造血干细胞移植后细胞因子Galectin-9和TGF-β的早期快速重建可以避免或减缓aGVHD的发生,移植后动态监测Tim-3^(+)CD4^(+)T细胞持续较多而血清中Galectin-9水平下降可能预示着aGVHD的发生。For probing into the changes of Tim-3/Galectin-9 negative signaling pathway in related HLA haploid peripheral blood hematopoietic stem cell transplantation and its clinical significance,36 patients underwent haploid hematopoietic stem cell transplantation and 20 healthy subjects were selected as the research objects.The levels of CD4^(+)T cells and Tim3 molecules in peripheral blood of patients and healthy control groups was monitored by flow cytometry,while the dynamic changes of cytokines Galectin-9,IFN-γ,IL-4,TGF-βand IL-17 in patients were monitored by ELISA before and after transplantation.According to the Seattle International Diagnostic Criteria,14 patients developed aGVHD after the transplantation,and 22 patients did not.Data also showed that after the transplantation,the percentage of CD4^(+)T cells in 30-90 days in patients without aGVHD was lower than that in the healthy control group.the serum levels of cytokines Galectin-9,TGF-β,IFN-γIL-4 and IL-17 in patients without aGVHD showed a trend of gradual increase,and the levels of Galectin-9 and TGF-βreached normal levels at 60 days after transplantation,while IFN-γ,IL-4 and IL-17 returned to normal levels on the 90th days after transplantation.The results of Spearman correlation analysis showed that Galectin-9 was positively correlated with the level of TGF-β.The percentage of Tim-3^(+)and CD4^(+)T cells and the levels of IFN-γand IL-17 in peripheral blood of patients with aGVHD were significantly higher than those of patients without aGVHD,while the levels of Galectin-9 and TGF-βin patients without aGVHD was higher.The results of Spearman correlation analysis showed that the percentage of Tim-3^(+)and CD4^(+)T cells was positively correlated with the level of IFN-γ.In conclusion,the early and rapid reconstitution of cytokines Galectin-9 and TGF-βafter haploid peripheral blood hematopoietic stem cell transplantation can avoid or slow down the occurrence of aGVHD.The continuous increase of Tim-3 and CD4^(+)T cells and the decrease of serum Gale

关 键 词：单倍体相合外周血造血干细胞移植 急性移植物抗宿主病 Tim-3/Galectin-9信号通路 负性调控 

分 类 号：R392[医药卫生—免疫学]