肝移植术后发生急性排斥反应受者淋巴细胞亚群的变化及意义

Changes and significance of lymphocyte subsets in recipients with acute rejection after liver transplantation

目的探讨肝移植受者术后发生急性排斥反应时淋巴细胞亚群的变化及意义。方法选取接受肝移植且发生急性排斥反应的受者作为排斥组(17例),利用倾向评分匹配方法按1∶1比例选取肝功能稳定的肝移植受者作为对照组(17例)。分析肝移植术后急性排斥反应的发生情况,对比两组受者他克莫司浓度。比较两组受者外周血淋巴细胞亚群的绝对值和比例,采用受试者工作特征(ROC)曲线分析淋巴细胞亚群对肝移植术后急性排斥反应发生的诊断价值。比较排斥组治疗前后淋巴细胞亚群绝对值和比例的变化。结果排斥组17例受者中,4例在术后28 d内发生急性排斥反应,13例在术后29~180 d发生急性排斥反应。两组他克莫司谷浓度差异无统计学意义(P=0.295)。与对照组比较,排斥组受者外周血T细胞、CD4+T细胞、B细胞和自然杀伤(NK)T细胞的比例均上升(均为P<0.05)。肝移植术后早期NKT细胞比例升高是肝移植术后发生急性排斥反应的独立危险因素[比值比(OR)1.774,95%可信区间(CI)1.059~2.971,P=0.029]。ROC曲线分析结果提示,CD4+T细胞、B细胞和NKT细胞比例的曲线下面积(AUC)分别为0.76、0.73和0.77。联用CD4+T细胞、B细胞和NKT细胞比例的AUC为0.89,当临界值为0.69时,灵敏度为0.706,特异度为0.941。排斥组所有受者治疗后均逐渐恢复,最终肝功能正常,治疗后T细胞、CD4+T细胞、CD8+T细胞和NK细胞比例均降低(均为P<0.05)。结论NKT细胞比例升高提示肝移植术后急性排斥反应发生风险增加,联用CD4+T细胞、B细胞和NKT细胞比例可早期发现和诊断肝移植术后急性排斥反应。

Objective To evaluate the changes and significance of lymphocyte subsets in the recipients with acute rejection after liver transplantation.Methods The recipients presenting with acute rejection after liver transplantation were assigned into the rejection group(n=17),and their counterparts with stable liver function were allocated into the control group(n=17)according to the ratio of 1∶1 by propensity score matching method.The incidence of acute rejection after liver transplantation was analyzed,and the concentration of tacrolimus in the recipients was compared between two groups.The absolute value and proportion of lymphocyte subsets in peripheral blood were compared between two groups.The diagnostic value of lymphocyte subsets for acute rejection after liver transplantation was assessed by the receiver operating characteristic(ROC)curve.The absolute value and proportion of lymphocyte subsets in the rejection group were compared before and after treatment.Results Among 17 recipients in the rejection group,4 cases developed acute rejection within postoperative 28 d,and 13 cases had acute rejection within postoperative 29-180 d.No significant difference was noted in the tacrolimus concentration between two groups(P=0.295).Compared with the control group,the proportions of peripheral blood T cells,CD4+T cells,B cells and natural killer(NK)T cells were significantly increased in the rejection group(all P<0.05).The elevated proportion of NKT cells in the early stage after liver transplantation was an independent risk factor for acute rejection following liver transplantation[odds ratio(OR)1.774,95%confidence interval(CI)1.059-2.971,P=0.029].ROC curve analysis showed that the area under curve(AUC)of CD4+T cells,B cells and NKT cells was 0.76,0.73 and 0.77,respectively.The AUC of combined use of CD4+T cells,B cells and NKT cells was 0.89,with a cut-off value of 0.69,sensitivity of 0.706 and specificity of 0.941.After corresponding treatment,all recipients were gradually recovered,and liver functions were eventually restored to normal in the rejection group.After treatment,the proportion of T cells,CD4+T cells,CD8+T cells and NK cells was significantly decreased(all P<0.05).Conclusions The elevated proportion of NKT cells indicates an increased risk of acute rejection after liver transplantation.Combined use of CD4+T cells,B cells and NKT cells may deliver early detection and diagnosis of acute rejection after liver transplantation.