肾移植术后急性排斥反应相关的T细胞受体免疫组库变化  

Study of T cell receptor in patients with acute rejection after renal transplantation

作　　者：张家兴 陈怀周[2] 赖柳生 王磊[2] 眭维国 Zhang Jiaxing;Chen Huaizhou;Lai Liusheng;Wang Lei;Sui Weiguo(Department of Nephrology, the Affiliated Guilin Hospital of Southern Medical University, Guilin 541002, China)

机构地区：[1]南方医科大学附属桂林医院肾脏科,桂林541002 [2]中国人民解放军第181医院肾脏科、全军器官移植与透析治疗中心、广西代谢性疾病研究重点实验室

出　　处：《中华肾脏病杂志》2018年第4期281-287,共7页Chinese Journal of Nephrology

基　　金：广西自然科学基金（2017GXNSFAA198185）;广西科技计划基地和人才专项重点实验室建设项目（16-380-66）;桂林市科学研究与技术开发计划项目（20170117-1）

摘　　要：目的为评估肾移植术后急性排斥患者的免疫状态，提高受者及移植物术后早期及远期存活率，本研究动态地检测急性排斥患者T细胞受体（TCR）的免疫组库变化。方法结合多重PCR扩增和高通量测序技术，动态分析肾移植过程中不同时间点的TCRB链互补决定区3（CDR3）的多样性和图谱特征。结果急性排斥患者的TCRCDR3的多样性在肾移植术后1d降至最低，在急性排斥发生前其多样性较术后1d上升，甚至超过术前水平。急性排斥反应发生前受者特异性上调的CDR3氨基酸序列被筛选出来。此外，急性排斥反应发生前存在TRBV、TRBJ基因亚家族的偏向取用，这可能与T细胞介导的对移植肾抗原的免疫识别和应答有关。结论肾移植术后急性排斥患者的免疫图谱的多样性降低，且TCRB链V和J亚家族呈现偏向取用的现象。Objective To evaluate the immune status of acute rejection recipients, and to improve the short- term and long-term survival rate of renal iransplant recipients and grafts, and to investigate dynamically the changes in the immune repertoire of patients with acute rejection. Methods Combined multiplex PCR amplification technique and high throughput sequencing technique, the TCR - chain complementarity determining region 3 （CDR3） diversity and repertoire characteristics at different time points during renal transplantation were analyzed, in order to reveal the immunological characteristics of T lymphocytes in patients with acute rejection. Results The diversity of TCR CDR3 in acute rejection patients was reduced to the lowest one day after surgery. The diversity of TCR CDR3 before acute rejection was higher than before. The acute rejection-related up- regulated TCR CDR3 amino acid sequences were screened out. In addition, TCR beta chain V and J subfamily showed the phenomenon of advantage usage in pre-acute rejection, which may be due to T cell recognition of transplanted kidney antigens in vivo. Conclusions The immune diversity of patients with acute rejection is significantly lower. In addition, TCR beta chain V and J subfamily show the phenomenon of advantage usage.

关 键 词：受体 抗原 T细胞 互补决定区 肾移植 移植物排斥 免疫组库 高通量测序 

分 类 号：R699.2[医药卫生—泌尿科学]