TIGIT在重症肌无力患者外周血NK细胞上的表达及意义  

Expression and significance of TIGIT in peripheral blood NK cells of patients with myasthenia gravis

作　　者：李凤展 李玲玲 王岩 王莹莹 张勇 LI Fengzhan;LI Lingling;WANG Yan;WANG Yingying;ZHANG Yong(Department of Neurology,the People′s Hospital of Jiawang District of Xuzhou City,Xuzhou,Jiangsu 221000,China;Department of Neurology,the Affiliated Hospital of Xuzhou Medical University,Xuzhou,Jiangsu 221002)

机构地区：[1]徐州市贾汪区人民医院神经内科,江苏徐州221000 [2]徐州医科大学附属医院神经内科,江苏徐州221002

出　　处：《徐州医科大学学报》2024年第12期888-893,共6页Journal of Xuzhou Medical University

基　　金：国家自然科学基金(81571579);徐州市卫生健康委科技项目(XWKYHT20210562)。

摘　　要：目的探究抑制性受体T细胞免疫球蛋白ITIM结构域(TIGIT)在重症肌无力(MG)患者外周血自然杀伤(NK)细胞中的表达及意义。方法收集来自徐州医科大学附属医院、徐州市贾汪区人民医院的34例初诊MG患者[其中全身型(GMG)16例,眼肌型(OMG)18例]及20例健康对照者的外周血样。采用定量重症肌无力评分(QMG)对34例MG患者进行评分,流式细胞术检测外周血NK细胞亚群及其表面受体TIGIT、穿孔素、颗粒酶B、滤泡辅助性T细胞(Tfh细胞)及其配体CD155、浆母细胞的表达水平,ELISA法检测乙酰胆碱受体抗体(AChR-Ab)滴度,分析各组TIGIT+NK细胞比例与Tfh细胞比例、浆母细胞比例、穿孔素、颗粒酶B、QMG评分、AChR-Ab滴度的相关性。结果与健康对照组比较,CD3-CD56+NK细胞在MG患者外周淋巴细胞中的比例下降(P<0.05),以CD56dimCD16+NK细胞亚群降低为主(P<0.05),且GMG组低于OMG组,差异有统计学意义(P<0.05)。CD56brightCD16-NK细胞比例在MG组和健康对照组外周血中的差异无统计学意义(P>0.05)。TIGIT在MG患者外周血NK细胞表面的表达水平高于健康对照组(P<0.001),且GMG组高于OMG组,差异有统计学意义(P<0.01)。MG患者外周Tfh细胞比例高于健康对照组(P<0.001),且GMG组高于OMG组(P<0.05),差异有统计学意义;与健康对照组相比,MG患者Tfh细胞表面配体CD155的表达比例升高(P<0.001),且GMG组高于OMG组,差异有统计学意义(P<0.01)。MG患者NK细胞分泌穿孔素、颗粒酶B能力低于健康对照组(P<0.05),且GMG组低于OMG组,差异有统计学意义(P<0.05)。与健康对照组相比,MG患者外周血浆母细胞比例升高(P<0.001),且以GMG组升高更为显著,差异有统计学意义(P<0.001)。TIGIT+NK细胞比例与Tfh细胞比例、QMG评分、AChR-Ab滴度、浆母细胞比例呈正相关(P<0.05),与颗粒酶B、穿孔素含量呈负相关(P<0.05)。结论MG患者NK细胞上TIGIT表达异常,且与NK细胞分泌穿孔素、颗粒酶B水平及疾病严重�Objective To investigate the expression and significance of the inhibitory receptor T-cell immunoglobulin and ITIM domain(TIGIT)on peripheral blood natural killer(NK)cells in patients with myasthenia gravis(MG).Methods A total of 34 initially diagnosed MG patients,including 16 patients with generalized MG(GMG)and 18 patients with ocular MG(OMG),and 20 healthy controls at the Affiliated Hospital of Xuzhou Medical University and the People′s Hospital of Jiangwa Distract of Xuzhou City were selected and their peripheral blood samples were collected.These 34 MG patients were evaluated by the Quantitative Myasthenia Gravis(QMG)scores.The NK cell subsets and surface markers(TIGIT,perforin and granzyme B),follicular helper T cells(Tfh cells)and their ligand CD155,and plasma cells were detected by flow cytometry.The acetylcholine receptor antibody(AChR-Ab)titer was measured by ELISA.The correlation between the proportion of TIGIT+NK cells and Tfh cell ratio,plasma cell ratio,perforin and granzyme B levels,QMG score,and AChR-Ab titer was analyzed.Results Compared with the healthy controls,MG patients showed decreases in the proportion of CD3-CD56+NK cells in the peripheral blood(P<0.05,P<0.001),primarily in the CD56dimCD16+NK cell subset(P<0.05),with the GMG group showing a greater reduction than the OMG group(P<0.05).The proportion of CD56brightCD16-NK cells did not show a significant difference between MG patients and healthy controls(P>0.01).The levels of TIGIT on NK cells in the peripheral blood of MG patients were significantly higher than those in the healthy control group(P<0.001),with the GMG group showing a greater increase than the OMG group(P<0.01).The proportion of Tfh cells in MG patients increased,compared with those in healthy controls(P<0.001),with the GMG group having a higher proportion than the OMG group(P<0.05).The expression of the Tfh cell surface ligand CD155 in MG patients significantly increased,compared with those in healthy controls(P<0.001),with the GMG group showing higher expression than th

关 键 词：重症肌无力 自然杀伤细胞 T细胞免疫球蛋白ITIM结构域 CD155 滤泡辅助性T细胞 

分 类 号：R746.1[医药卫生—神经病学与精神病学]