Objective: 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(+)CCR7(low)PD-1(high)) cells, Tfh (CD3(+)CD4(+)CD127(high)CD25(l)ow 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.
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（CCR7(low)PD-1(high) Tfh）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=0.000 4），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。.
Keywords: Anti-dsDNA antibody; Systemic lupus erythematosus; T follicular helper cell; systemic lupus erythematosus disease activity index.