滤泡辅助性T细胞与特发性视神经炎和视神经脊髓炎谱系疾病关系的研究  

Association of circulating T follicular helper cells with idiopathic optic neuritis and neuromyelitis optica spectrum disorders

作　　者：吴茜[1] 杨彬彬[1] 王佳伟[1] WU Qian;YANG Binbin;WANG Jiawei(Department of Neurology,Tong Ren Hospital of Capital Medical University,Beijing 100730)

机构地区：[1]首都医科大学附属北京同仁医院神经内科,100730

出　　处：《中国神经免疫学和神经病学杂志》2018年第2期91-96,共6页Chinese Journal of Neuroimmunology and Neurology

基　　金：首都医科大学附属北京同仁医院科研种子基金(2015-YJJ-ZZL021)

摘　　要：目的探讨滤泡辅助性T细胞(T follicular helper,Tfh)在特发性视神经炎(ON)和视神经炎谱系疾病(NMOSD)的体液免疫过程中的作用及其临床意义。方法选择2015-03—2017-04期间在作者科室住院的急性特发性ON患者41例(ON组)、NMOSD急性期患者55例(NMOSD组),患者均予甲基泼尼松龙冲击及序贯治疗,并行脑和脊髓MRI检查。于甲基泼尼松龙治疗前后进行扩展的神经功能障碍评分(EDSS)和视觉功能评分(VOS)检查;采用流式细胞术测定两组患者甲基泼尼松龙治疗前外周血和部分脑脊液Tfh标志物:包括辅助性T细胞(CD4)、趋化因子受体5(CXCR5)双阳性(CD4+CXCR5+)T细胞以及CD4、CXCR5、程序性死亡因子-1(PD-1)三阳性(CD4+CXCR5+PD-1+)T细胞占CD4+细胞的百分比(以下简称"比例");以ELISA法检测甲基泼尼松龙治疗前AQP-4抗体水平。以26名健康人为对照,检测其外周血CD4+CXCR5+、CD4+CXCR5+PD-1+T细胞比例。比较ON组和NMOSD组患者CD4+-CXCR5+及CD4+-CXCR5+-PD-1+T细胞比例、AQP4抗体水平及甲基泼尼松龙治疗前后EDSS和VOS功能评分变化,比较两患者组与健康对照组CD4+-CXCR5+和CD4+-CXCR5+-PD-1+T细胞比例,并分析患者血和脑脊液Tfh细胞比例的相关性,患者Tfh细胞比例与病程、年复发率、EDSS及VOS评分相关性,患者AQP4抗体水平与Tfh比例、病程和EDSS评分的相关性。结果ON组和NMOSD组外周血CD4+CXCR5+T细胞比例[分别为(16.69±4.78)%、(16.88±5.22%)]及CD4+CXCR5+PD-1+T细胞比例[分别为(10.61±3.44)%、(10.78±3.63)%]均显著高于健康对照组[分别为(12.60±4.57)%、(6.86±2.87)%,均P<0.01],两患者组间外周血和脑脊液Tfh细胞比例差异均无统计学意义(均P>0.05)。NMOSD组病程显著长于ON组[分别(27.23±37.78)、(12.06±32.02)个月,F=4.305,P<0.05],治疗前后EDSS评分均高于ON组(分别为治疗前3.94±1.03、3.06±1.15,F=15.11,P<0.01;治疗后3.43±1.47、2.50±1.58,F=8.836,P<0.01)。两组甲基泼尼松龙治疗后VOS评分(分别为5.17�Objective This study aimed to examine the potential role of T follicular helper(Tfh)cells in patients with idiopathic optic neuritis(ON)and neuromyelitis optica spectrum disorders(NMOSD).Methods The markers of Tfh cells,circulating CD4+CXCR5+and CD4<CXCR5<PI>1+T cells in 41 ON and 55 NMOSD patients as well as 26 healthy controls were examined by flow cytometry before treatment.Levels of serum aquaporrin-4(AQP4)antibody of the patients were also examined by ELISA.Expended Disability Status Scale(EDSS)and Visual Outcome Scale(VOS)were detected before and after treatment.Results The percentages of circulating CD4+CXCR5+and CD4+CXCR5+PD-1<Tfh cells among CD4+cells of ON and NMOSD patients were significantly increased compared with those of healthy controls(A〈0.01 respectively).No significant differences of Tfh cells in blood and cerebral spinal fluid(CSF)were found between ON and NMOSD patients.The ratio of CD4+CXCR5+T cells of CSF in NMOSD were positively correlated with that of blood(r=0.717,P=0.030).The serum AQP4 antibody of NMOSD patients were positively correlated with the time course of the diseases and EDSS score(r=0..18,r=0.351,P=0.000,P=0.001 respectively).The ratio of CD4+CXCR5+and CD4+CXCR5<PD-1+T cells of both ON and NMOSD were not correlated with the EDSS,VOS or annual recurrent rate.EDSS of the NMOSD patients was higher than that of the ON patients(P〈0.01).The time course ofNMOSD was longer than that ofON patients After methylprednisolone treatment,both EDSS and VOS significantly decreased compared with thosebefore treatment(P〈0.01 respectively).Conclusions T follicular helper cells may be involved in immune mechanisms of optic neuritis and neuromyelitis optica spectrum disorders.The serum AQP4 antibody of NMOSD is correlated with the patient conditions.

关 键 词：特发性视神经炎 视神经脊髓炎谱系病 滤泡辅助性T细胞 水通道蛋白4抗体 

分 类 号：R744.52[医药卫生—神经病学与精神病学]