摘要目的 通过检测滤泡辅助性T细胞(Tfh)亚型及效应型滤泡辅助性T细胞(Tfhem)在系统性红斑狼疮(SLE)患者外周血中的表达情况,深入探讨它们作为SLE病情活动指标的血液标志物的价值.方法 对象为2016年3月至2018年4月在北京大学人民医院风湿免疫科门诊或住院就诊的SLE患者64例及健康志愿者(正常对照)15名,应用流式细胞术检测SLE患者和正常对照者外周血中Tfh(CD3+CD4+CD45RA-CXCR5+)、细胞亚型Tfh1 (CXCR3+CCR6-Tfh)、Tfh2(CXCR3-CCR6+ Tfh)、Tfh17(CXCR3-CCR6+ Tfh)和Tfhem(CCR7lowPD-1highTfh)的表达.收集入组的SLE患者的临床资料及实验室检查指标,分析Tfh细胞亚型、Tfhem细胞与实验室指标、SLE疾病活动度和不同临床表型的相关性.结果 SLE患者外周血中Tfhem细胞的表达率明显高于正常对照组(1.40±1.12比0.51 ±0.24,P＜0.000 1),Tfhem细胞的表达与SLE病情活动度(SLEDAI) (P=0.015 3)、抗双链DNA抗体(anti-dsDNA antibody) (P=0.003 1)有显著相关性,与补体C3,补体C4,红细胞沉降率(ESR),C反应蛋白(CRP)无明显相关性.Tfh2的表达率明显高于正常对照组(3.83±2.74比2.18±1.07,P=0.0004),而Tfh1和Tfh17在两组中表达无明显差异,抗dsDNA抗体高的患者的Tfh2表达高于抗dsDNA抗体低的患者,但差异无统计学意义(4.33±3.20比3.70± 1.070,P=0.069 6).结论 Tfhem的表达与SLE的病情活动有关,有可能作为SLE病情进展及治疗效果的评价指标,Tfhem的表达同时与抗dsDNA抗体相关,因此,它在SLE发病过程抗体的生成中发挥着重要作用,甚至可能成为治疗SLE的靶细胞;Tfh2在SLE患者外周血中明显升高,与抗dsDNA抗体有一定的相关性,可能参与了SLE的病情进展.

abstractsObjective To investigate the role of T follicular helper (Tfh) subsets and T follicular helper effector memory (Tfhem) cells in circulation of patients with systemic lupus erythematosus (SLE),and explore their roles in SLE disease activity index as biomarkers.Methods This study enrolled 64 patients with SLE and 15 healthy controls.In peripheral blood from patients with SLE and health controls,the percentage of Tfhem (CD3+CD4+CD45RA-CXCR5+CCR7lowPD-1high) cells,Tfh (CD3+CD4+CD127highCD25low CD45RA-CXCR5+) subset:Tfh1 (CXCR3+CCR6-Tfh),Tfh2 (CXCR3-CCR6+ Tfh),Tfh17 (CXCR3-CCR6+ Tfh),were detected by flow cytometry.The correlations of Tfhem/Tfh subsets with clinical indicators which we collected were analyzed.Results The percentage of Tfhem was significantly increased in SLE patients compare to health controls (1.40± 1.12 vs 0.51±0.24,P＜0.000 1),and it was also correlated with systemic lupus erythematosus disease activity index (SLEDAI) (P=0.015 3) and anti-dsDNA antibody (P=0.003 1),but not with complement C3 (C3),complement C4 (C4),erythrocyte sedimentation rate (ESR),and C reaction protein (CRP).In addition,the percentage of Tfh2,but not Tfh1 or Tfh17,was significantly increased in SLE patients compare to health controls (3.83 ± 2.74 vs 2.18 ± 1.07,P=0.000 4).As compared to anti-dsDNA antibody＜25 group,the percentage of Tfh2 in anti-dsDNA antibody＞25 group was increased with no significant statistical difference (4.33 ± 3.20 vs 3.70 ± 1.070,P=0.069 6).Conclusion Our investigation show that Tfhem is associated with SLEDAI and it is a valuable evaluation biomarker for disease process and treatment.Meanwhile Tfhem is also associated with anti-dsDNA antibody,and it plays an important role in autoantibody production in SLE pathogenesis.Tfhem may be a good therapeutic target in SLE.For the meantime,the percentage of Tfh2 is significantly increased in SLE patients,and it had certain correlation with anti-dsDNA antibody,it might be involved in the development of SLE.