肾移植急性排斥受者外周血OX40 mRNA和Th1的变化及意义
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摘要
目的探讨外周血单个核细胞OX40 mRNA和外周血CD3+CD8-T辅助细胞(Th)1、Th2检测用于评估肾移植术后急性排斥的应用价值。方法收集2016年1月—2017年1月天津市第一中心医院器官移植中心行肾移植手术的40例肾移植受者及20名健康志愿者纳入研究,肾移植受者分为急性排斥组20例和肾功能稳定组20例。应用TaqMan实时荧光定量聚合酶链式反应(RT-PCR)定量检测3组外周血单个核细胞(PBMCs)中OX40 mRNA水平,应用流式细胞术检测外周血CD3+CD8-T淋巴细胞中IFN-γ(Th1)和IL-4(Th2)表达率。ROC曲线评价OX40和Th1对预测急性排斥的诊断价值。结果肾移植术后急性排斥组PBMCs中OX40 mRNA水平明显高于肾功能稳定组以及健康对照组(P<0.01),肾功能稳定组PBMCs中OX40 mRNA水平与健康对照组差异无统计学意义(P>0.05)。急性排斥组Th1表达率明显高于肾功能稳定组和正常对照组(P<0.01),3组Th2表达率差异无统计学意义(P>0.05)。OX40 mRNA诊断急性排斥反应的ROC曲线下面积(AUC)为0.903(95%CI:0.825～0.980);Th1的AUC为0.731(95%CI:0.587～0.874);两者联合诊断的AUC为0.930(95%CI:0.859～1.001)。结论监测肾移植受者外周血OX40mRNA及Th1细胞可以预测急性排斥反应。
Objective To investigate the significance of determining OX40 mRNA and Th1,Th2 of CD3+CD8-T helper lymphocytes in peripheral blood for evaluating renal acute rejection.MethodsA total of 40 recipients with renal transplantation and 20 healthy volunteers were enrolled and divided into acute rejection group(n=20) and stable renal allograft function group(n=20) according to the inclusion criteria. The levels of OX40 mRNA in peripheral blood mononuclear cells(PBMCs) were measured by TaqMan real-time reverse transcriptase-polymerase chain reaction(RTPCR) assays. The expression percentages of IFN-γ and IL-4 of CD3+CD8-T lymphocytes(Th1 and Th2) in peripheral blood were determined with flow cytometry. Receiver operating characteristic(ROC) curve was used to evaluate the prediction value.ResultsThe level of OX40 mRNA in PBMCs significantly elevated in acute rejection group compared with that in stable renal allograft function group and normal control group(P<0.01). There were no significant differences in OX40 mRNA levels between stable renal allograft function group and normal control group(P>0.05). The expression percentage of Th1 in peripheral blood was significantly higher in acute rejection group compared with that in stable renal allograft function group and normal control group(P<0.01). No significant difference was found in the expression percentage of Th2 in peripheral blood between the three groups(P>0.05). The area under ROC curve(AUC) in the diagnosis of acute rejection was 0.903(95% CI 0.825-0.980) for OX40 mRNA. The AUC of Th1 was 0.731(95%CI:0.587-0.874). The AUC of combined diagnosis was 0.930(95% CI: 0.859-1.001).ConclusionThe monitoring of OX40 mRNA and Th1 after renal transplantation can predict acute renal allograft rejection.
Objective To investigate the significance of determining OX40 mRNA and Th1,Th2 of CD3+CD8-T helper lymphocytes in peripheral blood for evaluating renal acute rejection.MethodsA total of 40 recipients with renal transplantation and 20 healthy volunteers were enrolled and divided into acute rejection group(n=20) and stable renal allograft function group(n=20) according to the inclusion criteria. The levels of OX40 mRNA in peripheral blood mononuclear cells(PBMCs) were measured by TaqMan real-time reverse transcriptase-polymerase chain reaction(RTPCR) assays. The expression percentages of IFN-γ and IL-4 of CD3+CD8-T lymphocytes(Th1 and Th2) in peripheral blood were determined with flow cytometry. Receiver operating characteristic(ROC) curve was used to evaluate the prediction value.ResultsThe level of OX40 mRNA in PBMCs significantly elevated in acute rejection group compared with that in stable renal allograft function group and normal control group(P<0.01). There were no significant differences in OX40 mRNA levels between stable renal allograft function group and normal control group(P>0.05). The expression percentage of Th1 in peripheral blood was significantly higher in acute rejection group compared with that in stable renal allograft function group and normal control group(P<0.01). No significant difference was found in the expression percentage of Th2 in peripheral blood between the three groups(P>0.05). The area under ROC curve(AUC) in the diagnosis of acute rejection was 0.903(95% CI 0.825-0.980) for OX40 mRNA. The AUC of Th1 was 0.731(95%CI:0.587-0.874). The AUC of combined diagnosis was 0.930(95% CI: 0.859-1.001).ConclusionThe monitoring of OX40 mRNA and Th1 after renal transplantation can predict acute renal allograft rejection.
引文
[1]Eikmans M,Gielis EM,Ledeganck KJ,et al.Non-invasive biomarkers of acute rejection in kidney transplantation:Novel targets and strategies[J].Front Med(Lausanne),2019,5:358.doi:10.3389/fmed.2018.00358.
[2]Willoughby J,Griffiths J,Tews I,et al.OX40:Structure and function-What questions remain?[J].Mol Immunol,2017,83:13-22.doi:10.1016/j.molimm.2017.01.006.
[3]李桂珍,张珩,赵俊芳,等.系统性红斑狼疮患者外周血T淋巴细胞激活状态及OX40、OX40L mRNA表达[J].中华皮肤科杂志,2012,45(11):818-819.Li GZ,Zhang H,Zhao JF,et al.Tlymphocytes activity and the expression of OX40,OX40L mRNA in peripheral blood of patients with systemic lupus erythematosus[J].Chin J Dermatol,2012,45(11):818-819.doi:10.3760/cma.j.issn.0412-4030.2012.11.020.
[4]Aspeslagh S,Postel-Vinay S,Rusakiewicz S,et al.Rationale for anti-OX40 cancer immunotherapy[J].Eur J Cancer,2016,52:50-66.doi:10.1016/j.ejca.2015.08.021.
[5]Webb GJ,Hirschfield GM,Lane PJ.OX40,OX40L and Autoimmunity:a comprehensive review[J].Clin Rev Allergy Immunol,2016,50(3):312-332.doi:10.1007/s12016-015-8498-3.
[6]Jensen SM,Maston LD,Gough MJ,et al.Signaling through OX40enhances antitumor immunity[J].Semin Oncol,2010,37(5):524-532.doi:10.1053/j.seminoncol.2010.09.013.
[7]Xu X,Huang H,Wang Q,et al.IFN-γ-producing Th1-like regulatory T cells may limit acute cellular renal allograft rejection:Paradoxical post-transplantation effects of IFN-γ[J].Immunobiology,2017,222(2):280-290.doi:10.1016/j.imbio.2016.09.012.
[8]李亚光,王凯,刘凯,等.肝移植术后半年内外周血Th1/Th2细胞因子变化[J].天津医药,2017,45(2):172-175.Li YG,Wang K,Liu K,et al.Changes of serum Th1/Th2 cytokines in peripheral blood pre-and post-liver transplantation[J].Tianjin Med J,2017,45(2):172-175.doi:10.11958/20161259.
[9]Xu X,Huang H,Wang Q,et al.IFN-γ-producing Th1-like regulatory T cells may limit acute cellular renal allograft rejection:Paradoxical post-transplantation effects of IFN-γ[J].Immunobiology,2017,222(2):280-290.doi:10.1016/j.imbio.2016.09.012.
[10]Mohammadi F,Solgi G,Tajik M,et al.Enzyme-Linked Immunosorbent Spot(ELISpot)monitoring of cytokine-producing cells for the prediction of acute rejection in renal transplant patients[J].Eur Cytokine Netw,2017,28(3):93-101.doi:10.1684/ecn.2017.0397.
[11]Liu T,Zhang Y,Shen Z,et al.Immunomodulatory effects of OX40Ig gene-modified adipose tissue-derived mesenchymal stem cells on rat kidney transplantation[J].Int J Mol Med,2017,39(1):144-152.doi:10.3892/ijmm.2016.2808.2019-02-122019-05-13
[2]Willoughby J,Griffiths J,Tews I,et al.OX40:Structure and function-What questions remain?[J].Mol Immunol,2017,83:13-22.doi:10.1016/j.molimm.2017.01.006.
[3]李桂珍,张珩,赵俊芳,等.系统性红斑狼疮患者外周血T淋巴细胞激活状态及OX40、OX40L mRNA表达[J].中华皮肤科杂志,2012,45(11):818-819.Li GZ,Zhang H,Zhao JF,et al.Tlymphocytes activity and the expression of OX40,OX40L mRNA in peripheral blood of patients with systemic lupus erythematosus[J].Chin J Dermatol,2012,45(11):818-819.doi:10.3760/cma.j.issn.0412-4030.2012.11.020.
[4]Aspeslagh S,Postel-Vinay S,Rusakiewicz S,et al.Rationale for anti-OX40 cancer immunotherapy[J].Eur J Cancer,2016,52:50-66.doi:10.1016/j.ejca.2015.08.021.
[5]Webb GJ,Hirschfield GM,Lane PJ.OX40,OX40L and Autoimmunity:a comprehensive review[J].Clin Rev Allergy Immunol,2016,50(3):312-332.doi:10.1007/s12016-015-8498-3.
[6]Jensen SM,Maston LD,Gough MJ,et al.Signaling through OX40enhances antitumor immunity[J].Semin Oncol,2010,37(5):524-532.doi:10.1053/j.seminoncol.2010.09.013.
[7]Xu X,Huang H,Wang Q,et al.IFN-γ-producing Th1-like regulatory T cells may limit acute cellular renal allograft rejection:Paradoxical post-transplantation effects of IFN-γ[J].Immunobiology,2017,222(2):280-290.doi:10.1016/j.imbio.2016.09.012.
[8]李亚光,王凯,刘凯,等.肝移植术后半年内外周血Th1/Th2细胞因子变化[J].天津医药,2017,45(2):172-175.Li YG,Wang K,Liu K,et al.Changes of serum Th1/Th2 cytokines in peripheral blood pre-and post-liver transplantation[J].Tianjin Med J,2017,45(2):172-175.doi:10.11958/20161259.
[9]Xu X,Huang H,Wang Q,et al.IFN-γ-producing Th1-like regulatory T cells may limit acute cellular renal allograft rejection:Paradoxical post-transplantation effects of IFN-γ[J].Immunobiology,2017,222(2):280-290.doi:10.1016/j.imbio.2016.09.012.
[10]Mohammadi F,Solgi G,Tajik M,et al.Enzyme-Linked Immunosorbent Spot(ELISpot)monitoring of cytokine-producing cells for the prediction of acute rejection in renal transplant patients[J].Eur Cytokine Netw,2017,28(3):93-101.doi:10.1684/ecn.2017.0397.
[11]Liu T,Zhang Y,Shen Z,et al.Immunomodulatory effects of OX40Ig gene-modified adipose tissue-derived mesenchymal stem cells on rat kidney transplantation[J].Int J Mol Med,2017,39(1):144-152.doi:10.3892/ijmm.2016.2808.2019-02-122019-05-13