Liang Y C, Yao Y, Zhang R J, Shao M, Sun X L, Shi G X, Gao C, Yu D, He J
Department of Rheumatology and Immunology, First Affiliated Hospital of Xiamen University, Xiamen 361003, China.
Department of Gastrointestinal Surgery, Tongji Hospital of Tongji Medical College of Huangzhong Uninversity of Science & Technology, Wuhan 430000, China.
Zhonghua Yi Xue Za Zhi. 2019 Jan 15;99(3):164-168. doi: 10.3760/cma.j.issn.0376-2491.2019.03.002.
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. 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. The percentage of Tfhem was significantly increased in SLE patients compare to health controls (1.40±1.12 vs 0.51±0.24, 0.000 1), and it was also correlated with systemic lupus erythematosus disease activity index (SLEDAI) (0.015 3) and anti-dsDNA antibody (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, 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, 0.069 6). 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.
为探讨滤泡辅助性T细胞(Tfh)亚群及循环滤泡辅助性效应记忆T细胞(Tfhem)在系统性红斑狼疮(SLE)患者中的作用,并探索它们作为生物标志物在SLE疾病活动指数中的作用。本研究纳入了64例SLE患者和15名健康对照者。在SLE患者和健康对照者的外周血中,通过流式细胞术检测Tfhem(CD3(+)CD4(+)CD45RA(-)CXCR5(+)CCR7(low)PD-1(high))细胞、Tfh(CD3(+)CD4(+)CD127(high)CD25(l)ow CD45RA(-)CXCR5(+))亚群:Tfh1(CXCR3(+)CCR6(-)Tfh)、Tfh2(CXCR3(-)CCR6(+) Tfh)、Tfh17(CXCR3(-)CCR6(+) Tfh)的百分比。分析Tfhem/Tfh亚群与我们收集的临床指标之间的相关性。与健康对照者相比,SLE患者中Tfhem的百分比显著升高(1.40±1.12 vs 0.51±0.24,P<0.0001),并且它还与系统性红斑狼疮疾病活动指数(SLEDAI)(P=0.0153)和抗双链DNA抗体(P=0.0031)相关,但与补体C3(C3)、补体C4(C4)、红细胞沉降率(ESR)和C反应蛋白(CRP)无关。此外,与健康对照者相比,SLE患者中Tfh2的百分比显著升高(3.83±2.74 vs 2.18±1.07,P=0.0004),而Tfh1或Tfh17则无显著变化。与抗双链DNA抗体<25组相比,抗双链DNA抗体>25组中Tfh2的百分比升高,但无显著统计学差异(4.33±3.20 vs 3.70±1.070,P=0.0696)。我们的研究表明,Tfhem与SLEDAI相关,是疾病进程和治疗的有价值评估生物标志物。同时,Tfhem也与抗双链DNA抗体相关,在SLE发病机制中的自身抗体产生中起重要作用。Tfhem可能是SLE的一个良好治疗靶点。同时,SLE患者中Tfh2的百分比显著升高,且与抗双链DNA抗体有一定相关性,可能参与了SLE的发生发展。