Objective To investigate the possible role of T help cell 17 (Th17 cell) and T regulation cell (Treg cell) balance in the pathogenesis of rheumatoid arthritis (RA) and rheumatoid arthritis-associated interstitial lung dis-ease (RA-ILD). Methods From October 2015 to October 2016, 42 patients with RA (RA group) and 38 patients with RA-ILD from Taihe Hospital of Shiyan City were enrolled, as well as 40 healthy controls (Control group). RA disease activity score in 28 joints (DAS28), rheumatoid factor (RF), blood Sedimentation (ESR), high sensitive-C reactive pro-tein (hs-CRP), lung function and other clinical parameters were examined and recorded for patients with RA. Flow cy-tometry (FCM) was used for all subjects to analyze the ratio of Th17 cells and Treg cells in peripheral blood mononu-clear cell (PBMc), Real time quantitative polymerasechain reaction (RT-PCR) was used to analyze the expression of forkhead-winged-helix family transcription factor p3 (Foxp3) and retinoid-related orphan nuclearγt (ROR)-γt mRNA in PBMc, and the relationship about Th17/Treg cell balance between ILD was also analyzed. T-test and Chi-square test were used for inter-group comparison. Pearson's linear analysis and logistic regression were used for correlation analy-sis. Results ①The ratio of Th17 cells in peripheral blood of RA-ILD group was (3.11±1.32)%, which was significant-ly increased compared with (2.34±0.72)%in the RA group and (1.12±0.33)%in the control group (both P<0.05);the ra-tio of Treg cells in the RA group was (3.73±0.64)%, and in the RA-ILD group was (3.53±0.84)%, both significantly de-creased compared with (5.83 ± 1.55)% in the control group. However, there was no significant difference between the RA-ILD group and the RA group (P>0.05). The proportion of Th17/Treg cells in the RA-ILD group was (0.88 ± 0.31), which was significantly increased compared with (0.54 ± 0.16) in the RA group and (0.38 ± 0.11) in the control group (both P<0.05).②The expression of ROR-γt mRNA in the RA-ILD group was (13.12±3.73), which was significantly increased compared with (8.31±3.72) in the RA group and (4.12±1.22) in the control group (both P<0.01), along with a decrease of Foxp3 mRNA expression in RA-ILD group (1.24±0.55) compared with the RA group (2.53±1.14) and the control group (3.74±1.25) (both P<0.05).③Pearson correlation analysis indicated that Th17 cells was negatively cor-related with Treg cells (r=-0.342, P=0.013), and ROR-γt mRNA was negatively correlated with Foxp3 in RA-ILD group (r=-0.413, P<0.01).④According to logistic regression analysis, the risk factors of carbon monoxide diffusing ca-pacity (DLCO) in RA-ILD patients were the level of Th17 cells, the ratio of Th17/Treg, DAS28 and disease duration (all P<0.01). Conclusion Th17 cell is increased while Treg cell is decreased in RA-ILD patients. The change of Th17/Treg cells ratio are important for the pathogenesis of RA-ILD and could aggravate the damage of lung function.%目的 探讨辅助性T细胞17(Th17细胞)和调节性T细胞(Treg细胞)平衡在类风湿关节炎(RA)及其相关性肺间质疾病(ILD)发病机制中可能的作用.方法 纳入2015年10月至2016年10月在十堰市太和医院收治的42例RA患者(RA组),38例合并肺间质疾病的RA患者(RA-ILD组)和40例健康者(对照组)作为研究对象;监测并记录所有患者RA 28关节疾病活动评分(DAS28)、类风湿因子(RF)、血沉(ESR)、超敏C反应蛋白(hs-CRP)及肺功能等临床资料.采用流式细胞仪技术测定所有受试者外周血单个核细胞(PBMc)中Th17细胞和Treg细胞的比例,荧光定量PCR技术检测相应的转录因子维甲酸相关孤核受体(ROR-γt)和叉头螺旋翼状转录因子3(Foxp3)mRNA表达水平,并分析Th17/Treg细胞平衡与肺间质疾病的关系.统计学处理采用t检验和方差分析,相关性分析采用Pearson直线相关分析和Logistic回归分析.结果 ①在外周血中,RA-ILD组Th17细胞比例为(3.11±1.32)%,同RA组[(2.34±0.72)%]及对照组[(1.12±0.33)%]比较均有明显增高,差异具有统计学意义(P<0.05);RA-ILD组外周血Treg细胞比例为(3.53±0.84)%,RA组为(3.73±0.64)%,均较对照组[(5.83±1.55)%]明显降低,差异具有统计学意义(P<0.05),但RA-ILD组与RA组比较差异无统计学意义(P>0.05);RA-ILD组Th17/Treg细胞比例为(0.88±0.31),较RA组(0.54±0.16)和对照组(0.38±0.11)显著增高,差异均具有显著统计学意义(P<0.01);②RA-ILD组患者的ROR-γt mRNA表达水平为(13.12±3.73),较RA组的(8.31±3.72)及对照组(4.12±1.22)显著升高,差异均具有显著统计学意义(P<0.01),而RA-ILD组患者的Foxp3 mRNA表达水平为(1.24±0.55),明显低于RA组的(2.53±1.14)和对照组的(3.74±1.25),差异均具有统计学意义(P<0.05);③Pearson直线相关分析显示,RA-ILD组患者的Th17细胞与Treg细胞比例呈负相关(r=-0.342,P=0.013),ROR-γt mRNA与Foxp3 mRNA呈负相关(r=-0.413,P<0.01);④Logistic回归分析显示,Th17细胞、Th17/Treg细胞比值、DAS28评分及病程对RA-ILD患者一氧化碳弥散量(DLCO)有显著影响(P<0.05).结论 RA患者体内Th17细胞明显增多且伴随Treg细胞减少,Th17/Treg细胞比例失衡可能参与RA-ILD的发生及发展,并导致患者肺功能的恶化.
展开▼
