淋巴细胞亚群与肾移植术后感染及排斥反应的关系

Relationship between lymphocyte subsets with infection and rejection after renal transplantation

目的 动态监测肾移植受者外周血淋巴细胞亚群的变化,探讨淋巴细胞亚群变化与感染或排斥反应的关系.方法 前瞻性收集2015年6月至2016年12月间肾移植受者和同期亲属活体供肾者淋巴细胞亚群数据.以流式细胞分析仪检测供者术前,受者术前和术后1、2、4周以及术后2、3、4、5、6个月外周血淋巴细胞（Lym）计数、T淋巴细胞（T细胞）计数、CD4^＋ T淋巴细胞（CD4^＋细胞）计数、CD8^＋T淋巴细胞（CD8^＋细胞）计数、B淋巴细胞（B细胞）计数、自然杀伤细胞（NK细胞）计数、CD4^＋细胞/CD8^＋细胞比值.结果 本研究共纳入健康成年亲属活体肾者64名（健康对照组）和肾移植受者351例（术前组）,其中术后发生感染者67例（术后感染组）,术后发生急性排斥反应46例（术后排斥组）,术后稳定者238例（术后稳定组）.术前组的Lym、T细胞、CD4^＋细胞、CD8^＋细胞、B细胞、NK细胞明显低于健康对照组（P〈0.05）.术后稳定组与健康对照组各淋巴细胞亚群计数及CD4^＋细胞/CD8^＋细胞比值的集中频率分布差异显著（P〈0.05）,术后稳定组各指标的集中频率分布范围如下：Lym为1 000~1 500/μl,T细胞〈1 500/μl,CD4^＋细胞〈1 000/μl,CD8^＋细胞〈1 000/μl,B细胞〈300/μl,NK细胞为100~300/μl,CD4^＋细胞/CD8^＋细胞比值为0.5~1.0.术后感染组在感染前Lym、T细胞、NK细胞计数较明显下降,低于术后稳定组（P〈0.05）;感染期Lym、T细胞、CD4^＋细胞、CD8^＋细胞、B细胞、NK细胞计数均低于术后稳定组（P〈0.05）;感染控制后1个月,各指标逐渐恢复至术后稳定组水平;T细胞、CD4^＋细胞、CD8^＋细胞、B细胞与感染高度相关.术后排斥组在排斥反应发生前CD4^＋细胞、CD4^＋细胞/CD8^＋细胞开始升高,明显高于术后稳定组（P〈0.05）;排斥反应发生时,T细胞、CD4^＋细胞、CD4^＋细胞/CD8^＋细胞较术后稳定组明显升高（P〈0.05）;冲击治疗1周时,T细胞、CD4^＋细胞、CD8^＋细胞、B细胞、NK细胞计数均低于稳定组（P〈0.05）;排斥反应逆转后,各指标逐步恢复至术后稳定组水平;T细胞、CD4^＋细胞、CD8^＋细胞与排斥反应高度相关.经Logistic回归分析,T细胞、CD4^＋细胞、CD8^＋细胞、B细胞、CD4^＋细胞/CD8^＋细胞比值为术后发生感染或排斥反应相关的独立因素.结论 淋巴细胞亚群的动态监测对预测肾移植受者的感染和排斥反应发生具有一定意义,CD4^＋细胞和CD4^＋细胞/CD8^＋细胞比值为独立危险因素.

Objective To dynamically monitor the changes of peripheral blood lymphocyte subsets of renal transplant recipients and investigate the relationship between lymphocyte subsets with infection and rejection.Methods The clinical data of allogenic kidney transplantation recipients and living relative donors in the Department of Kidney Transplantation of the First Affiliated Hospital of Zhengzhou University were prospectively collected from June 2015 to December 2016.The data of lymphocyte subsets and other related indexes were obtained from renal transplant recipients and relatives of the same period.Results Sixty-four cases of living-relative donors and 351 cases of renal transplant recipients were enrolled in this study,and the recipients were divided into 3 groups：infection group （67 cases）,acute rejection group （46 cases）,and stable group （238 cases）,according to the diagnostic criteria.There was significant difference in the concentration distribution of lymphocytes between the stable group and the control group （P〈0.05）.The stable frequency distribution range of the stable group was as follows （cells/μL）：Lym （1 000-1 500）,T （〈1 500）,CD4^＋ （〈1 000）,CD8^＋ （〈1 000）,B （〈300）,NK （100-300）,CD4^＋/CD8^＋ （0.5-1.0）.The number of Lym,T,CD4^＋,CD8^＋,NK and B cells in the preoperative patients was less than that in the healthy population （P〈0.05）;The number of Lym,T,CD4^＋, CD8^＋,B and NK cells was gradually decreased in the postoperative infection group,which was less than that in the stable group （P〈0.05）.After treatment the indicators gradually restored to the level in the stable group level;the number of T,CD4^＋,CD8^＋,B cells was highly correlated with infection.The number of T and CD4^＋ cells,and CD4^＋/CD8^＋ ratio were significantly increased in acute rejection group as compared with the stable group,and gradually decreased after the rejection was reversed.The number of T,CD4^＋,CD8^＋ cells was highly correlated with rejection.Lymphocyte subsets had a predictive effect on infection and rejection of recipients,and CD4^＋ cell count and CD4^＋/CD8^＋ ratio were independent risk factors.Conclusion The monitoring of lymphocyte subsets has an important clinical value in the evaluation of immune status and individual treatment of renal recipients.