蛋白糖蛋白A重复序列活化态Tregs细胞对类风湿性关节炎的影响及机制

The effects of GARP activated Tregs cells on rheumatoid arthritis and its mechanism

目的探究蛋白糖蛋白A重复序列(glycoprotein A repetitions predominant,GARP)活化态Tregs细胞对类风湿性关节炎(rheumatoid arthritis,RA)的影响及机制。方法选取232例RA患者和240例健康志愿者,收集临床资料,ELISA法检测RF、anti-CCP和CRP含量;流式细胞术检测外周血中GARP^+Tregs比例,并做Pearson相关性分析;q-PCR法检测FoxP3 mRNA含量;ELISA检测外周血中IL-17A、TGF-β1、IFN-γ和IL-4含量。结果RA患者抗CCP、RF和CRP含量和ESR均明显高于健康志愿者;RA组GARP^+Tregs,TGF-β1和FoxP3 mRNA含量明显低于健康志愿者;IL-4含量明显降低,IFN-γ含量显著升高;Th1/Th2指数和IL-17A含量显著高于健康志愿者组;RA患者的CRP水平和ERS与外周血GARP^+Tregs比例变化具有明显负相关性;与Th1/Th2指数变化具有明显正相关性。结论GARP^+Tregs比例变化可能指示RA的发生发展,可能通过调控Th1/Th2细胞反应平衡向Th2应答方向发展,及自身与Th17反应平衡参与调节RA病变的作用。

Objective To investigate the effects of GARP activated Tregs cells on rheumatoid arthritis (RA)and its mechanism.Methods A total of 232 patients and 240 healthy volunteers were enrolled.Clinical data were collected.ELISA was used to measure RF,anti-CCP and CRP.The percentage of GARP^+Tregs in peripheral blood(PB)was analyzed by flow cytometry with Pearson correlation analysis performed afterwards.FoxP3 mRNA level was measured by q-PCR.PB IL-17A,TGF-β1,IFN-γ and IL-4 content were measured by ELISA.Results The anti-CCP,RF and CRP levels and ERS in RA patients were significantly higher than those in healthy volunteers;GARP^+Tregs,TGF-β1 and FoxP3 mRNA levels in RA group were significantly lower than those in healthy volunteers;IL-4 content decreased,IFN-γ content increased significantly;Th1/Th2 index and IL-17A content was significantly higher than the healthy volunteer group.CRP level and ERS were significant negative correlated with PB GARP^+Tregs and Th1/Th2 index.Conclusion GARP^+Tregs ratio may indicate the development of RA,which may be related to the development of Th2 response by regulating the balance of Th1/Th2 cell response,and the balance with Th17 response in regulating the pathological changes of RA.