目的 通过检测类风湿关节炎(RA)患者外周血滤泡辅助性T细胞(Tfh)和细胞因子白细胞介素(IL)-21,CXCL13的表达并与健康者比较,探讨其与RA临床表现的相关性及其可能的免疫学发病机制.方法 流式细胞仪检测患者和健康对照外周血中Tfh细胞的变化；酶联免疫吸附试验( ELISA)法检测RA患者及健康对照者血浆中IL-21、CXCL13等细胞因子的水平.采用t检验、单因素方差分析和SNK-q检验、z2检验、Spearman秩和相关分析以及多元线性回归分析.结果 RA患者外周血中Tfh比例显著高于对照组(3.0±1.2与1.1±0.4,P＜0.01)；同时RA患者轻、中、重度活动组外周血Tfh的比例依次增多(1.8+0.7,2.5±0.6与4.0+1.2),3组之间比较差异均有统计学意义(P均＜0.01),且均较对照组升高(P＜0.01)；Tfh细胞数与RA患者DAS28、红细胞沉降率(ESR)、C反应蛋白(CRP)、关节压痛数、骨质破坏、RF及抗环瓜氨酸肽(CCP)抗体滴度呈正相关；严重骨质破坏组Tfh表达率明显高于轻度或无骨质破坏组(2.7+1.1与3.4±1.3)；未治疗组相比非正规治疗组、正规治疗组的Tfh表达率逐渐降低(P均＜0.01)；正规治疗组的Tfh表达率低于非正规治疗组(P＜0.05).重、中、轻度活动组及健康对照者组的IL-21、CXCL13水平依次降低(P均＜0.05).结论 RA患者外周血Tfh比例及IL-21、CXCL13水平显著升高,且与疾病活动、骨侵蚀等有明显相关,抗风湿药物治疗可以降低Tfh,提示Tfh细胞可能在RA发病中起着重要作用.%Objective To test the level of cell factor interleukin (IL)-21,CXCL13 in the plasma of patients with rheumatoid arthritis (RA),and to analyze the relationship between Follicular helper T cells(Tfh)and clinic features and discuss the possible immunological pathogenesis of RA.Methods The Tfh cells were obtained from patients and healthy controls (NC) and detected by Flow cytometery.While the levels of IL-21,CXCL13 in patients and NC were measured by ELISA tests.Those analysis were performed by student's t-test,one-way ANOVA,SNK-q test,Chi-square test,Spearman's correlation and multiple linear regression.Results The expression of CD4+CXCR5+ICOS+ cells (Tfh) in PBMCs of RA was significantly higher than normal controls (3.0±1.2 vs 1.1±0.4,P＜0.01).Meanwhile,the three RA groups of patients were divided to low,moderate and high disease activity groups,and the results showed that the expression of Tfh were increased accordingly (1.8±0.7,2.5±0.6,4.0±1.2).The expression of Tfh in the three groups were all significantly higher than that of controls (P＜0.01).There was a positive correlation between Tfh and DAS28,ESR,CRP,TJC,and bone erosion,RF and anti-CCP respectively.The expression of Tfh in those patients who had bone destruction was higher than those with no or mild bone destructions (2.7±1.1vs 3.4±1.3).The expression of Tfh in patients with un-treated RA patients,when compared to those RA patients who were treated appropriately and those who were not treated appropriately,was decreased significantly.The expression of Tfh in appropriately treated RA patients was lower than that without appropriately treatment.The level of IL-21,CXCL13 was decreased in patients with RA in the order of high,moderate,low disease activity and NC.Conclusion The expression of Tfh and the levels of IL-21,CXCL13 are increased significantly,and are closely related to disease activity and bone ersions.The expression of Tfh is decreased after relevant treatment.These results indicate that the abnormality of Tfh may play an important role in the pathogenesis of RA.
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