类风湿关节炎患者外周血TFH细胞TIGIT和PD1表达及意义  

Expression of TIGIT and PD1 on TFH from RA patients and clinical significance

作　　者：黄自坤[1] 张露 李雪[1] 罗清[1] Huang Zikun;Zhang Lu;Li Xue;Luo Qing(Dept of Clinical Laboratory,First Affiliated Hospital of Nanchang University,Nanchang 330006)

机构地区：[1]南昌大学第一附属医院检验科,南昌330006

出　　处：《安徽医科大学学报》2023年第5期838-844,共7页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:82160307);江西省重点研发计划项目(编号:20181BBG70013);江西省卫生健康委科技计划(编号:202130158);江西省自然科学基金(编号:20171BAB205113)。

摘　　要：目的探讨含T细胞免疫球蛋白和酪氨酸免疫抑制受体结构域蛋白(TIGIT)和程序性死亡分子(PD1)在类风湿关节炎(RA)患者外周血滤泡辅助性T(TFH)细胞上的表达及其临床意义。方法应用流式细胞仪检测79例RA患者(RA组)和45例对照者(HC组)外周血TFH细胞TIGIT和PD1阳性的百分率和平均荧光强度(MFI),并进行比较,分析其与RA实验室检查指标的相关性。结果①与HC组相比,RA组仅PD1^(+)TFH细胞百分率和PD1表达MFI增高,差异有统计学意义(P<0.01)。②RA组TIGIT^(+)PD1^(-)TFH细胞百分率低于HC组(P<0.01);RA组TIGIT^(+)PD1^(+)TFH细胞百分率、PD1表达MFI和TIGIT^(-)PD1^(+)TFH细胞百分率、PD1表达MFI高于HC组(P<0.05)。③RA组外周血TIGIT^(+)PD1^(+)TFH细胞PD1表达MFI与类风湿因子(RF)呈正相关(P<0.05),TIGIT^(-)PD1^(+)TFH细胞百分率、TIGIT^(-)PD1^(+)TFH细胞和TIGIT^(+)PD1^(+)TFH细胞PD1表达MFI均与阳性的RF呈正相关(P<0.05)。④RA组外周血TIGIT^(+)PD1^(-)TFH细胞百分率与血沉(ESR)呈负相关(P<0.05),TIGIT^(-)PD1^(+)TFH细胞百分率与ESR呈正相关(P<0.05),TIGIT^(+)PD1^(+)TFH细胞百分率与淋巴细胞数量(Lym)呈负相关(P<0.05),TIGIT^(+)PD1^(+)TFH细胞PD1表达MFI与淋巴细胞百分比(Lym%)呈负相关、与中性粒细胞数量(Net)、中性粒细胞百分比(Net%)、中性粒细胞与淋巴细胞比值(NLR)、系统性免疫炎症指数(SII)、衍生中性粒细胞与淋巴细胞比值(dNLR)、ESR、C-反应蛋白(CRP)呈正相关(P<0.05),TIGIT^(-)PD1^(+)TFH细胞PD1表达MFI与Net、ESR、CRP呈正相关(P<0.05)。⑤RA组外周血TIGIT^(+)PD1^(-)TFH细胞百分率与疾病活动性评分(DAS28)-ESR呈负相关(P<0.05),TIGIT^(+)PD1^(+)TFH细胞PD1表达MFI和TIGIT^(-)PD1^(+)TFH细胞PD1表达MFI均与DAS28-ESR、DAS28-CRP、关节压痛数(PJC)、关节肿痛数(SJC)、视觉模拟评分(VAS)呈正相关(P<0.05)。⑥TIGIT^(+)PD1^(-)TFH细胞百分率降低和TIGIT^(+)PD1^(+)TFH细胞百分率升高为RA发病的危险因素。结论RA患者外周Objective To investigate the expression of T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain(TIGIT)and programmed death 1(PD1)on follicular T helper cells(TFH)from the patients with rheumatoid arthritis(RA)and to analyze the clinical relevance to disease severity.Methods The expression of TIGIT and PD1 on TFH cells were examined from 79 RA patients and 45 healthy controls(HC)by the technique of flow cytometry.The expression of TIGIT and PD1 including percentage of TIGIT^(+)TFH,PD1^(-)TFH,TIGIT^(+)PD1^(-)TFH,TIGIT^(+)PD1^(+)TFH,TIGIT^(-)PD1^(+)TFH cells and the mean fluorescence intensity(MFI)on theses TFH cells were compared between RA patients and HC.Moreover,its correlation with laboratory inspection was analyzed.Results①The percentage of PD1^(+)TFH and the MFI of PD1 on PD1^(+)TFH from RA patients significantly increased compared with HC(P<0.01).②The percentage of TIGIT^(+)PD1^(-)TFH significantly decreased compared with HC(P<0.01),whereas the percentage of TIGIT^(+)PD1^(-)TFH,the MFI of PD1 on TIGIT^(+)PD1^(-)TFH,the percentage of TIGIT^(+)PD1^(+)TFH and the MFI of PD1 on TIGIT^(+)PD1^(+)TFH significantly increased(P<0.05).③The MFI of PD1 on TIGIT^(+)PD1^(+)TFH in RA patients was positively associated with rheumatoid factors(RF)(P<0.05).The percentage of TIGIT^(-)PD1^(+)TFH,the MFI of PD1 on TIGIT^(-)PD1^(+)TFH,the MFI of PD1 on TIGIT^(+)PD1^(+)TFH in RA patients were positively associated with increased RF(P<0.05).④The percentage of TIGIT^(+)PD1^(-)TFH in RA patients was negatively associated with erythrocyte sedimentation rate(ESR)(P<0.05).The percentage of TIGIT^(-)PD1^(+)TFH in RA patients was positively associated with ESR(P<0.05).The percentage of TIGIT^(+)PD1^(+)TFH in RA patients was negatively associated with lymphocyte count(Lym)(P<0.05).The MFI of PD1 on TIGIT^(+)PD1^(+)TFH in RA patients was negatively associated with lymphocyte percentage(Lym%),and positively associated with neutrophil count(Net),neutrophil percentage(Net%),neutrophilto-lymphocyte ratio(NLR),

关 键 词：类风湿关节炎 TFH细胞 PD1 T细胞免疫球蛋白和酪氨酸免疫抑制受体结构域蛋白 

分 类 号：R593.22[医药卫生—内科学]