重症肌无力患者CD4^(+)T细胞中转录因子Foxp1表达的初步探讨

Expression of transcription factor Foxp1 in CD4^(+)T cells of patients with myasthenia gravis

目的探讨重症肌无力(MG)患者外周血CD4^(+)T细胞中转录因子Foxp1 mRNA的表达及他克莫司免疫治疗前后Foxp1 mRNA的表达变化。方法前瞻性选择郑州大学第一附属医院神经内科自2018年1月至2020年1月收治的MG患者26例(MG组)和自2018年1月至2019年6月门诊健康体检者18例(正常对照组)进入研究。采用重症肌无力定量评分(QMGs)评估MG患者的疾病严重程度。于MG患者治疗前、治疗后6个月,正常对照者入组后即刻,抽取受试者外周静脉血15 mL,采用免疫磁珠法分选外周血单个核细胞(PBMC)中的CD4^(+)T细胞,采用实时荧光定量PCR(RT-qPCR)检测2组受试者CD4^(+)T细胞中Foxp1 mRNA的表达。采用Spearman相关性检验分析MG患者CD4^(+)T细胞中Foxp1 mRNA的表达与QMGs评分、血清抗乙酰胆碱受体(AchR)抗体浓度的相关性。结果26例MG患者中眼肌型MG(oMG)10例,全身型MG(gMG)16例;伴胸腺瘤7例,胸腺增生2例,胸腺正常17例。与正常对照组(1.051±0.364)比较,MG组患者CD4^(+)T细胞中Foxp1 mRNA的表达(0.692±0.257)明显下降,差异有统计学意义(P<0.05)。gMG患者CD4^(+)T细胞中Foxp1 mRNA的表达较oMG患者明显下降,差异有统计学意义(P<0.05)。MG患者接受他克莫司单药治疗6个月后CD4^(+)T细胞中Foxp1 mRNA的表达较治疗前明显升高,差异有统计学意义(P<0.05)。相关性分析显示MG患者治疗前CD4^(+)T细胞中Foxp1 mRNA的表达与QMGs评分呈负相关关系(r=-0.438,P=0.025)。结论MG患者CD4^(+)T细胞中Foxp1 mRNA的表达下降,其表达水平与疾病严重程度呈负相关,且在一定程度上可以反应他克莫司免疫治疗的疗效。

Objective To investigate the transcript factor Foxp1 mRNA expression in peripheral blood CD4^(+)T cells of patients with myasthenia gravis(MG),and the changes of Foxp1 mRNA expression before and after tacrolimus immunotherapy.Methods A prospective study was performed.Twenty-six MG patients admitted to our hospital from January 2018 to January 2020 and 18 healthy controls accepted physical examination in our hospital from January 2018 to July 2019 were recruited.Quantitative myasthenia gravis score(QMGs)was used to assess MG severity.Peripheral blood mononuclear cells(PBMCs)were isolated from the peripheral venous blood of MG patients before treatment and 6 months after treatment,and healthy controls right after enrollment by density gradient centrifugation;CD4^(+)T cells were isolated from PBMCs by magnetic cell separation.The Foxp1 mRNA expression was detected by real-time fluorescent quantification PCR(RT-qPCR).Spearman's correlation coefficient was used to evaluate the correlations of Foxp1 mRNA expression with QMGs and serum acetylcholine receptor(AchR)antibody concentration in all subjects.Results In the 26 MG patients,there were 10 with ocular MG and 16 with general MG;7 patients were with thymoma,2 were with thymic hyperplasia,and 17 were with normal thymus.The Foxp1 mRNA expression in CD4^(+)T cells of MG patients(0.692±0.257)was significantly decreased as compared with that in the heathy controls(1.051±0.364,P<0.05).Moreover,the Foxp1 mRNA expression in general MG patients was significantly lower than that in ocular MG patients(P<0.05).The Foxp1 mRNA expression in MG patients 6 months after acrolimus monotherapy was significantly increased as compared with that before treatment(P<0.05).There was a negative correlation between Foxp1 mRNA expression and QMGs(r=-0.438,P=0.025).Conclusion Transcript factor Foxp1 mRNA expression is downregulated in CD4^(+)T cells of MG patients,and its expression is negatively correlated with MG severity,which can reflect the effect of tacrolimus monotherapy on MG to some extent.