类风湿关节炎患者血清IL-25表达水平与疾病活动度的相关性分析及机制研究

Correlation analysis and mechanism research of serum IL-25 expression level and disease activity in patients with rheumatoid arthritis

目的探讨类风湿关节炎(RA)患者白细胞介素-25(IL-25)表达水平与疾病活动度及炎性因子白细胞介素-6(IL-6)、白细胞介素-17A(IL-17A)、肿瘤坏死因子-α(TNF-α)的相关性,以及IL-25对T细胞分泌IL-17A及转录因子ROR-γt的调控。方法选取2017年10月至2019年12月于我院就诊的50例RA患者作为观察组,同时间段选取50例健康体检者作为对照组。比较观察组与对照组的IL-25水平;分析IL-25水平与28个关节数疾病活动度评分(DAS28)、红细胞沉降率(ESR)、C反应蛋白(CRP)、IL-6、IL-17A、TNF-α的相关性;另外观察IL-25干预前、后对CD4+T细胞细胞因子IL-17A及转录因子ROR-γt mRNA的影响。结果观察组的IL-25水平明显高于对照组(P<0.001)。中/高疾病活动组的IL-25水平明显高于低疾病活动组(P<0.001)。观察组的IL-25水平与DAS28评分及ESR、CRP水平呈正相关(P<0.0001)。观察组的IL-25水平与IL-6、IL-17A及TNF-α水平呈正相关(P<0.0001)。RA组的IL-17A、IL-17A mRNA、ROR-γt mRNA水平显著高于RA+rhIL-25组、HCs组(P<0.01)。结论RA患者的血清IL-25表达水平显著升高,特别是中/高疾病活动度患者,提示IL-25水平与RA患者疾病严重程度和免疫炎性反应密切相关;同时,IL-25还具有抑制CD4+T细胞向Th17分化的作用。

Objective To investigate the correlation between the expression level of interleukin-25(IL-25)and disease activity and inflammatory factors interleukin-6(IL-6),interleukin-17A(IL-17A)and tumor necrosis factor-α(TNF-α)in patients with rheumatoid arthritis(RA),and the regulation of IL-25 on the secretion of IL-17A and transcription factor ROR-γt by T cells.Methods Fifty patients with RA who were treated in our hospital from October 2017 to December 2019 were selected as the observation group,and 50 healthy subjects were selected as the control group at the same time.The level of IL-25 in the observation group and the control group was compared.The correlation between IL-25 level and 28-joint Disease Activity Scores(DAS28),erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),IL-6,IL-17A and TNF-αwas analyzed.In addition,the effects of IL-17A and ROR-γt mRNA on CD4+T cells were observed before and after IL-25 intervention.Results The level of IL-25 in the observation group was significantly higher than that in the control group(P<0.001).The level of IL-25 in the moderate/high disease activity group was significantly higher than that in the low disease activity group(P<0.001).The level of IL-25 in the observation group was positively correlated with DAS28 score and the levels of ESR and CRP(P<0.0001).The level of IL-25 in the observation group was positively correlated with the levels of IL-6,IL-17A and TNF-α(P<0.0001).The levels of IL-17A,IL-17A mRNA and ROR-γt mRNA in the RA group were significantly higher than those in the RA+rhIL-25 group and the HCs group(P<0.01).Conclusion The expression level of serum IL-25 in RA patients was significantly increased,especially in patients with moderate/high disease activity,suggesting that the level of IL-25 was closely related to the severity of disease and immune inflammatory response in RA patients;at the same time,IL-25 also has the effect of inhibiting the differentiation of CD4+T cells into Th17.