造血干细胞移植后免疫重建早期T细胞受体删除环的检测分析  

Measurements of T-cell receptor excision cycles in early stage of immune reconstitution after hematopoietic stem cell transplantation

作　　者：王坤 韩俊永 陈金烟 刘慎敏 薛士杰 金静君 Wang Kun;Han Jun-yong;Chen Jin-yan;Liu Shen-min;Xue Shi-jie;Jin Jing-jun(Immunology Research Institute of Fujian Academy of Medical Sciences,Fujian Provincial Key Laboratory of Medical Analysis,Fuzhou 350001,Fujian Province,China)

机构地区：[1]福建省医学科学研究院免疫研究所,福建省医学测试重点实验室,福建省福州市350001

出　　处：《中国组织工程研究》2018年第29期4643-4649,共7页Chinese Journal of Tissue Engineering Research

基　　金：福建省属公益类科研院所基本科研专项(2014R1031-2);福建省医学创新课题(2016-CXB-2)。

摘　　要：背景:目前对于造血干细胞移植后的免疫监测缺乏直接明确的检测指标,利用不断改良的实时定量荧光PCR技术监测T细胞受体删除环(T-cell receptor excision circle,TREC或signal joint T-cell receptor excision circle,sjTREC)拷贝数来反映胸腺新近功能,从而评估免疫重建水平,指导预后治疗。目的:检测造血干细胞移植患者免疫重建早期T细胞受体删除环水平,分析移植方式、年龄、疾病类型、性别等因素的影响。方法:采用Taq Man探针,实时定量荧光PCR技术检测29例健康正常人,19例造血干细胞移植前患者,6例造血干细胞移植后患者的外周血1 000个细胞中所含sjTREC拷贝数。结果与结论:(1)正常对照组1 000个细胞中所含sjTREC拷贝数为26.99±29.3,随年龄增加而降低,男女性别sjTREC水平无明显差异;患者组移植前sjTREC水平低于正常对照组且差异有显著性意义(P=0.006);(2)6例患者移植后1个月时sj TREC水平上升,移植后6个月时sjTREC水平下降;(3)移植后6个月时2例HLA半相合亲缘移植与4例HLA全相合非亲缘移植患者sjTREC水平接近;(4)结果表明,移植前患者胸腺功能严重受损,在移植后1个月出现短暂上升后下降的趋势可能与胸腺应激性反应相关;亲缘与非亲缘移植、男性与女性、不同年龄患者等单因素分析未见明显差异,但移植后sjTREC水平上升反映了移植后胸腺新近输出功能的变化,体现了免疫重建受多种因素的影响。BACKGROUND:Currently,there is no direct and explicit detection index for immune surveillance after hematopoietic stem cell transplantation.The copy number of T-cell receptor excision circle(TREC or signal joint T-cell receptor excision circle,sjTREC)that reflects the recent function of the thymus is monitored by using constantly improved real-time quantitative PCR technology,thereby assessing the level of immune reconstitution and guiding prognosis treatments.OBJECTIVE:To analyze the influence of transplantation approach,type of diseases,age,and sex in early stage of immune reconstitution after hematopoietic stem cell transplantation by investigating the level of sjTREC in the peripheral blood.METHODS:The number of sjTREC copies per 1 000 cells in the peripheral blood in control group(n=29),before-group(n=19),and after-group(n=6)were detected using absolute quantitative real-time PCR with TaqMan probes.RESULTS AND CONCLUSION:In the 1 000 cells,the number of sjTREC copies in the control group was 26.99±29.3 and it decreased with age but no difference existed between male and female.Compared with the control group,the level of sjTREC was significantly lowered in the before-group(P=0.006).After transplantation,the level of sjTREC was rapidly increased within 1 month,and then decreased at 6 months.No obvious differences were found in the level of sjTREC after half-matched HLA related donor transplantation in two cases and full-matched HLA unrelated donor transplantation in four cases.All the findings indicate that the thymus function in patients is seriously impaired before transplantation,and the changes of sjTREC copies that are transiently increased and then decreased at 1 month after transplantation may be related to the stress response of the thymus in the early immune reconstitution period.Although there are no differences between related and unrelated donors,male and female,or different ages,the increased level of sjTREC reflects the changes of thymus function after transplantation,indicating that a variety o

关 键 词：T细胞受体删除环 异基因造血干细胞移植 免疫重建 胸腺功能 干细胞 造血干细胞移植 基因重排 T淋巴细胞 胸腺 组织工程 

分 类 号：R394.2[医药卫生—医学遗传学]