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  • 康子健△,刘亚群△,张志国,刘耀阳,徐沪济*.CCR7loPD-1hi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[J].第二军医大学学报,2018,39(11):1202-1208    [点击复制]
  • KANG Zi-jian△,LIU Ya-qun△,ZHANG Zhi-guo,LIU Yao-yang,XU Hu-ji*.Proportion of CCR7loPD-1hi follicular helper T cell in peripheral blood of systemic lupus erythematosus patients and its clinical role[J].Acad J Sec Mil Med Univ,2018,39(11):1202-1208   [点击复制]
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CCR7loPD-1hi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
康子健△,刘亚群△,张志国,刘耀阳,徐沪济*
0
(海军军医大学(第二军医大学)长征医院风湿免疫科, 上海 200003
共同第一作者
*通信作者)
摘要:
目的 检测系统性红斑狼疮(SLE)患者外周血中CCR7loPD-1hi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CCR7loPD-1hi Tfh和CCR7hiPD-1lo Tfh的比例。分析SLE患者外周血中CCR7loPD-1hi 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,CCR7loPD-1hi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CCR7loPD-1hi 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CCR7loPD-1hi 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CCR7loPD-1hi 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CCR7loPD-1hi 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。
关键词:  系统性红斑狼疮  滤泡辅助性T细胞  CCR7受体  程序性死亡蛋白1  类风湿关节炎  干燥综合征
DOI:10.16781/j.0258-879x.2018.11.1202
投稿时间:2018-07-24修订日期:2018-10-09
基金项目:国家自然科学基金青年科学基金(81302578).
Proportion of CCR7loPD-1hi follicular helper T cell in peripheral blood of systemic lupus erythematosus patients and its clinical role
KANG Zi-jian△,LIU Ya-qun△,ZHANG Zhi-guo,LIU Yao-yang,XU Hu-ji*
(Department of Rheumatology and Immunology, Changzheng Hospital, Navy Medical University(Second Military Medical University), Shanghai 200003, China
Co-first authors.
* Corresponding author)
Abstract:
Objective To explore the proportion of CCR7loPD-1hi follicular helper T cell (Tfh) in peripheral blood of the patients with systemic lupus erythematosus (SLE) and its clinical role. Methods Peripheral blood samples were collected from 31 SLE patients, 29 rheumatoid arthritis (RA) patients, 12 Sjögren's syndrome (SS) patients and 37 healthy controls. Flow 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 CCR7loPD-1hi Tfh and CCR7hiPD-1lo Tfh in peripheral blood. The correlation between the proportion of CCR7loPD-1hi Tfh in peripheral blood 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 CCR7loPD-1hi Tfh compared with those of the CCR7hiPD-1lo Tfh (t=3.73, 5.06 and 8.27; all P<0.01). The frequencies of CCR7loPD-1hi Tfh in the peripheral blood of the SLE and RA patients were 5.79% (2.97%, 8.95%) and 4.57% (2.51%, 7.60%), respectively, which 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 CCR7loPD-1hi Tfh in peripheral blood between SS patients and healthy controls (U=183.0, P>0.05). The proportion of CCR7loPD-1hi Tfh in peripheral blood 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 CCR7loPD-1hi Tfh in peripheral blood 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, which is of great significance for diagnosis, monitoring and prognosis of SLE.
Key words:  systemic lupus erythematosus  follicular helper T cells  CCR7 receptors  programmed death 1  rheumatoid arthritis  Sjögren's syndrome