类风湿关节炎患者外周血调节性T细胞数目变化及其与疾病活动的相关性分析

Correlation between the changes of regulatory T cells in peripheral blood and disease activity measures in rheumatoid arthritis

目的探讨调节性T细胞在RA外周血中的变化,评估其与疾病活动的相关性,以期进一步阐明调节性T细胞在RA发生发展中的重要意义。方法选取2016年1月至2018年9月本院诊治的300例RA患者及性别、年龄相匹配的100名健康人群,收集所有RA患者的疾病活动度相关指标。采用改进的流式细胞术检测所有受试者外周血调节性T细胞、辅助性T(Th)17细胞及二者比值,并用独立样本t检验或秩和检验进行组间比较,2组计量资料的相关性分析采用Spearman秩相关检验。结果RA组调节性T细胞绝对计数[(26±17)个/μl]与百分比[(4.4±2.0)%]相比于健康对照组[(35±13)个/μl,(5.1±1.5)%]均显著下降(t=4.815,P<0.01;t=4.111,P<0.05),Th17细胞的数目(t=1.114,P=0.266)与百分比(t=1.577,P=0.116)无明显改变。与健康对照组[(35±13)个/μl]相比,初治[RA组(31±17)个/μl,t=1.974,P=0.049]与复诊RA组[(24±16)个/μl,t=5.978,P<0.01]患者的调节性T细胞绝对计数均显著下降,而复诊RA患者下降得更为明显(t=3.453,P<0.01)。随着DAS28水平的增加,外周血调节性T细胞绝对计数呈现下降趋势[疾病稳定组(33±15)个/μl,低活动组(31±17)个/μl,中活动组(28±17)个/μl,高活动组(24±16)个/μl],调节性T细胞绝对计数与DAS28(r=-0.139,P=0.016)、ESR(r=-0.116,P=0.046)呈负相关。结论调节性T细胞绝对计数在RA患者外周血中显著下降,这或许是由于疾病本身直接引起而不仅仅是免疫抑制药物的影响。调节性T细胞数目缺陷或许是RA疾病发生发展的重要免疫机制,这为评估患者病情、探索新的有效治疗方案提供重要临床依据。

Objective To investigate the level of regulatory T(Treg)cells of peripheral blood and evaluate the correlation between Treg cells and disease activity in rheumatoid arthritis(RA)to further clarify the role of Treg cells in the pathogenesis of RA.Methods The participants included 300 patients with RA,from the Second Hospital of Shanxi Medical University between January 2016 and September 2018 and 100 gender and age matched healthy individuals.The absolute numbers and proportion of Treg cells and helper T(Th)17 cells and the ratio of Th17/Treg in peripheral blood of these individuals were detected by flow cytometry combined with standard absolute counting beads.Main statistical analysis methods were t test,spearman correlation and rank sum test.Results Patients with RA had lower absolute numbers[(35±13)cells/μl vs(26±17)cells/μl,t=4.815,P<0.01]and percentage[(5.1±1.5)%vs(4.4±2.0)%,t=4.111,P<0.01]of Treg cells compared with those in healthy controls,while the number(t=1.114,P=0.266)and proportion(t=1.577,P=0.116)of Th17 cells were not significantly changed.RA patients,regardless of new onset(no prior treatment)or treatment with immunosuppressants,had significantly lower absolute numbers of Treg cells[healthy controls(35±13)cells/μl;the Treg cells in new onset patients was(31±17)cells/μl,t=1.974,P=0.049;Treg cells in treated patients was(24±16)cells/μl,t=5.978,P<0.01]but not Th17 cells than healthy controls.With the increase of disease activity score uses 28 joint counts(DAS28),the absolute counts of peripheral Treg cells trended to decrease[remission group(33±15)cells/μl,low activity group(31±17)cells/μl,moderate activity group(28±17)cells/μl,high activity group(24±16)cells/μl],and were negatively correlated with DAS28(r=-0.139,P=0.016)and erythrocyte sedimentation rate(ESR)(r=-0.116,P=0.046).Conclusion The absolute counts of peripheral Treg cells decreased significantly,which are associated directly with the pathogenesis of RA rather than high-dose glucocorticoids or immunosuppressive agents.Changes in circulating Treg cells number may play a prominent role in the disease process of RA,which provides clinical basis for evaluation of disease activity and exploration of new effective therapies.