CCR7^(lo)PD-1^(hi)滤泡辅助性T细胞在系统性红斑狼疮患者外周血中的比例及临床意义

Proportion of CCR7^(lo)PD-1^(hi) follicular helper T cell in peripheral blood of systemic lupus erythematosus patients and its clinical role

目的检测系统性红斑狼疮(SLE)患者外周血中CCR7^(lo)PD-1^(hi)滤泡辅助性T细胞(Tfh)的比例,并探讨其临床意义。方法收集31例SLE患者、29例类风湿关节炎(RA)患者、12例干燥综合征(SS)患者和37名健康对照的外周血样本。采用流式细胞术检测Tfh表面C-X-C趋化因子受体3(CXCR3)、诱导型共刺激分子(ICOS)和信号淋巴细胞激活分子家族成员5(SLAMF5)的表达水平,以及外周血中CCR7^(lo)PD-1^(hi)Tfh和CCR7hiPD-1lo Tfh的比例。分析SLE患者外周血中CCR7^(lo)PD-1^(hi) Tfh的比例与临床指标、成浆细胞比例的相关性。结果相比CCR7hiPD-1lo Tfh,CCR7^(lo)PD-1^(hi)表面CXCR3、ICOS和SLAMF5的表达水平较高(t=3.73、5.06、8.27,P均<0.01)。SLE和RA患者外周血中CCR7^(lo)PD-1^(hi) Tfh的比例分别为5.79%(2.97%,8.95%)和4.57%(2.51%,7.60%),均高于健康对照组[2.93%(1.63%,5.21%),U=314.5、332.5,P均<0.01],而SS患者外周血中CCR7^(lo)PD-1^(hi) Tfh的比例与健康对照相比差异无统计学意义(U=183.0,P>0.05)。SLE患者外周血中CCR7^(lo)PD-1^(hi) Tfh的比例与系统性红斑狼疮疾病活动指数(SLEDAI)、抗双链DNA抗体滴度、成浆细胞比例均呈正相关(r=0.447 1、0.517 4、0.466 9,P均<0.05)。结论 SLE患者外周血中CCR7^(lo)PD-1^(hi) Tfh比例增加与SLEDAI升高和成浆细胞比例的增加相关,检测患者外周血Tfh亚群可间接反映生发中心及B淋巴细胞的功能状态,对SLE的诊断、监测和预后有重要意义。

Objective To exp^lore the proportion of CCR7^loPD-1^hi follicular helper T cell(Tfh)in peripheral b^lood of the patients with systemic lupus erythematosus(SLE)and its clinical role.Methods Peripheral b^lood samples were collected from 31 SLE patients,29 rheumatoid arthritis(RA)patients,12 Sj?gren’s syndrome(SS)patients and 37 healthy controls.F^low cytometry was used to detect the expression levels of C-X-C chemokine receptor 3(CXCR3),inducible costimulator(ICOS)and signaling lymphocytic activation molecule family member 5(SLAMF5)on surface of Tfh,and the frequencies of CCR7^loPD-1^hi Tfh and CCR7^hiPD-1^lo Tfh in peripheral b^lood.The correlation between the proportion of CCR7^loPD-1^hi Tfh in peripheral b^lood of SLE patients and clinical indicators and the proportion of plasmablasts was analyzed.Results The expression levels of CXCR3,ICOS and SLAMF5 were significantly^higher on the surface of the CCR7^loPD-1^hi Tfh compared with those of the CCR7^hiPD-1^lo Tfh(t=3.73,5.06 and 8.27;all P<0.01).The frequencies of CCR7^loPD-1^hi Tfh in the peripheral b^lood of the SLE and RA patients were 5.79%(2.97%,8.95%)and 4.57%(2.51%,7.60%),respectively,w^hich were both significantly^higher than that of the healthy controls(2.93%[1.63%,5.21%],U=314.5 and 332.5,both P<0.01).There was no difference in the frequency of CCR7^loPD-1^hi Tfh in peripheral b^lood between SS patients and healthy controls(U=183.0,P>0.05).The proportion of CCR7^loPD-1^hi Tfh in peripheral b^lood of the SLE patients was positively correlated with systemic lupus erythematosus disease activity index(SLEDAI),serum anti-double-stranded DNA(dsDNA)titers and the proportion of plasmablasts(r=0.447 1,0.517 4 and 0.466 9;all P<0.05).Conclusion Increased proportion of CCR7^loPD-1^hi Tfh in peripheral b^lood of the SLE patients is associated with increased SLEDAI and increased proportion of plasmablasts;and detecting the Tfh subsets can indirectly reflect the functional status of germinal center and B lymphocytes,w^hich is of great significance for diagnosis,monitoring and prognosis of SLE.