Chinese Journal of Contemporary Neurology and Neurosurgery ›› 2020, Vol. 20 ›› Issue (9): 779-787. doi: 10.3969/j.issn.1672-6731.2020.09.005

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Polymorphism of peripheral blood T cell receptor β chain variable region in patients with clinically isolated syndrome

WU Yan1, ZHANG Ji-hong2, DONG Hui-qing1, LI Da-wei1, LIU Zheng1, WAN Sui-gui3   

  1. 1 Department of Neurology, Beijing Xuanwu Hospital, Capital Medical University, Beijing 100053, China;
    2 Department of Neurology, the Affiliated Brain Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China;
    3 Department of Hematology, Beijing Xuanwu Hospital, Capital Medical University, Beijing 100053, China
  • Received:2020-09-16 Online:2020-09-25 Published:2020-09-30
  • Supported by:

    This study was supported by Beijing Municipal Science and Technology Commission (No. Z131100006813020).

临床孤立综合征患者外周血T细胞受体β链可变区多态性研究

吴岩1, 张纪红2, 董会卿1, 李大伟1, 刘峥1, 万岁桂3   

  1. 1 100053 北京, 首都医科大学宣武医院神经内科;
    2 210029 南京医科大学附属脑科医院神经内科;
    3 100053 北京, 首都医科大学宣武医院血液科
  • 通讯作者: 董会卿,Email:shshtt@sina.com
  • 基金资助:

    北京市科技计划课题(项目编号:Z131100006813020)

Abstract:

Objective To investigate the polymorphism of T cell receptor β chain variable region (TCRVβ) in peripheral blood of clinically isoiated syndrome (CIS) patients. To preliminarily predict the specific TCRVβ fragment of CIS and its diagnostic value for CIS. Methods Hospitalized patients of Beijing Xuanwu Hospital from September 2012 to March 2014, were divided into 2 groups including CIS group (experimental pateints, n=30) and normal control group (healthy volunteers, n=30). The routine immune indexes and expression of TCRVβ subfamilies were detected by flow cytometry. CELL Quest Pro 5.1 software was used to analyze 24 subfamilies of TCRVβ. Calculated the statistic of amplification rate, amplification number and amplification fraction of the total 24 subfamilies of TCRVβ. Results Compared to the normal control group, the quantitative expression of CD4+ TCRVβ2, 4, 5.2, 5.3, 7.1, 8, 14, 17, 20, 21.3 and CD8+TCRVβ4, 14 were significantly expanded in CIS group, CD4+TCRVβ11 and CD8+TCRVβ9, 11 were significantly reduced in CIS group (P<0.05 or P<0.01). The amplification rate of CD4+TCRVβ2 (P=0.002) and CD8+TCRVβ14 (P=0.010) in CIS group were higher than those in normal control group, but there was no significant difference in the other subfamilies. There was no statistical difference in the expansion rate of the TCRVβ between CIS group and normal control group. The amplification number (P=0.001) and amplification fraction (P=0.006) of the TCRVβ in CIS group were significantly higher than the normal control group. Receiver operating characteristic curve (ROC) analysis indicated that the area under the curve (AUC) of CD4+TCRVβ4 in the diagnosis of CIS was 0.719 (95%CI:0.592-0.851, P=0.003). The sensitivity was 83.33%, the specificity was 56.67%. The AUC of CD4+ TCRVβ14 in the diagnosis of CIS was 0.713 (95% CI:0.581-0.845, P=0.005). The sensitivity was 70%, the specificity was 56.23%. The AUC of CD8+TCRVβ4 in the diagnosis of CIS was 0.727 (95%CI:0.600-0.854, P=0.002). The sensitivity was 93.33%, the specificity was 50%. The three fragments have medium diagnostic value for CIS. Conclusions Although the expression levels of CD4+ TCRVβ4, CD4+ TCRVβ14 and CD8+ TCRVβ4 in peripheral blood are increased in CIS group, their diagnostic value is limited.

Key words: Demyelinating diseases, Receptors, antigen, T-cell, alpha-beta, Polymorphism, genetic, Flow cytometry

摘要:

目的 分析临床孤立综合征患者外周血T细胞受体β链可变区(TCRVβ)多态性,初步预测特异性TCRVβ片段,研究其对临床孤立综合征的诊断价值。方法 选择2012年9月至2014年3月诊断并接受治疗的临床孤立综合征患者30例(CIS组),以同期行健康体检的30例受试者为正常对照组。流式细胞术检测常规免疫学指标和TCRVβ亚家族表达变化,CELL Quest Pro 5.1等相关软件分析24个TCRVβ亚家族成员表达水平,并计算扩增者比例、扩增个数和扩增分数。结果 TCRVβ 24个亚家族中,CIS组CD4+TCRVβ2、4、5.2、5.3、7.1、8、14、17、20、21.3片段,以及CD8+TCRVβ4、14片段表达水平高于正常对照组,而CD4+TCRVβ11和CD8+TCRVβ9、11片段表达水平低于正常对照组(P<0.05或P<0.01)。CIS组CD4+TCRVβ2(P=0.002)和CD8+TCRVβ14(P=0.010)扩增者比例均高于正常对照组,其余亚家族扩增者比例差异则无统计学意义(均P>0.05)。CIS组TCRVβ扩增者比例与正常对照组差异无统计学意义(P>0.05),但扩增个数(P=0.001)、扩增分数(P=0.006)均高于正常对照组。受试者工作特征(ROC)曲线显示,CD4+TCRVβ 4诊断临床孤立综合征的曲线下面积(AUC)为0.719(95% CI:0.592~0.851,P=0.003),灵敏度83.33%、特异度56.67%;CD4+TCRVβ14诊断的AUC为0.713(95% CI:0.581~0.845,P=0.005),灵敏度70%、特异度56.23%;CD8+TCRVβ4诊断的AUC为0.727(95% CI:0.600~0.854,P=0.002),灵敏度93.33%、特异度50%;以上3个片段对临床孤立综合征均具有中等诊断价值。。结论 虽然临床孤立综合征患者外周血CD4+TCRVβ4、CD4+TCRVβ14和CD8+TCRVβ4片段表达水平升高,但其诊断价值有限。

关键词: 脱髓鞘疾病, 受体, 抗原, T细胞, &alpha, -&beta, 多态现象, 遗传, 流式细胞术