类风湿关节炎患者血清IL-35的水平及其与疾病活动度的关系

The levels of serum interleukin 35 in patients with rheumatoid arthritis and its correlation with disease activity

目的探讨类风湿关节炎(RA)患者血清IL-35表达水平与疾病活动度的相关性。方法选取确诊RA患者118例,分为活动期组62例和缓解期组56例。同时选取90例健康人作为对照,ELISA法检测RA患者及对照者血清IL-35水平,实时荧光定量PCR检测外周血单个核细胞(PBMC)中IL-35亚基EBI3和P35 mRNA表达水平。分析血清IL-35水平与DAS28评分、C反应蛋白(CRP)、红细胞沉降率(ESR)、类风湿因子(RF)、关节肿胀数(SJC)和关节压痛数(TJC)等的相关性。结果活动期组RA患者血清中IL-35浓度(38.09±16.90)pg/m L显著低于对照组[(82.25±15.82)pg/m L,P<0.01)]和缓解期组[(72.96±11.74)pg/m L,P<0.01)];依据DAS28评分将活动期组RA患者分为轻度、中度和重度组,血清IL-35水平(pg/m L)在3组中依次降低(轻度60.95±7.31,中度39.68±9.51,重度28.02±9.16),轻度组与中度或重度组间差异具有统计学意义(P<0.05)。活动期组和缓解期组患者血清IL-35水平与SJC、CRP和DAS28评分呈负相关性(P<0.05),与ESR、TJC、RF无相关性。PBMC中P35 mRNA在RA活动期组中显著降低,低于健康对照组和缓解期组(0.47±0.18 vs 1.91±1.12&1.82±0.53,P<0.01),但EBI3 mRNA在活动期组(1.62±0.68)、缓解期组(1.48±0.77)及对照组(1.86±1.21)中差异无统计学意义(P>0.05)。结论活动期组RA患者血清IL-35水平显著下降,且伴随P35 mRNA水平下降,并与RA疾病活动度密切相关,可作为RA疾病活动度评价的潜在指标。

Objective To investigate the correlation of serum interleukin 35（ IL-35） levels with disease activity in the patients with rheumatoid arthritis（ RA）. Methods 118 patients with RA,including 62 in active stage and 56 in remission stage,and 90 healthy controls were enrolled in our study. The levels of serum IL-35 were detected by ELISA,and the mRNA expression levels of subunits epstein-barr virus induced 3（ EBI3） and P35 of IL-35 in peripheral blood mononuclear cells（ PBMC） were determined by real-time quantitative PCR. The correlations of serum IL-35 levels with clinical parameters such as DAS28 score,C-reactive protein（ CRP）,erythrocyte sedimentation rate（ ESR）,rheumatoid factor（ RF）,swollen joint count（ SJC） and tender joint count（ TJC） were analyzed. Results The levels of serum IL-35 in patients with active RA [（ 38. 09 ± 16. 90） pg / m L] were significantly lower than those in remission RA patients [（ 72. 96 ± 11. 74） pg / m L] and healthy controls [（ 82. 25 ± 15. 82） pg / m L]（ P〈0. 01）. When the active RA patients were divided into mild,moderate and severe RA based on DAS28 score,their serum IL-35 levels reduced in turn at this sequence（ 60. 95 ± 7. 31） pg / m L,（ 39. 68 ± 9. 51） pg / m L and（ 28. 02 ± 9. 16） pg / m L,and the former significantly higher than the later two（ P〈0. 05）. The serum IL-35 levels in active and remission RA patients were negatively correlated with SJC,CRP levels and DAS28 score（ P〈0. 05）,but not related to ESR,TJC and RF levels. The p35 mRNA levels in PBMC of active RA patients（ 0. 47 ±0. 18） were significantly lower than those in remission RA patients（ 1. 82 ± 0. 53） and healthy controls（ 1. 91 ± 1. 12）（ P〈0. 01）,while there was no significant difference in mRNA levels of EBI3 among the three groups（ 1. 62 ± 0. 68,1. 48 ± 0. 77 and 1. 86 ±1. 21,P〉0. 05）. Conclusion The serum IL-35 and the related p35 mRNA levels decreased significantly in active RA patients,and were closely correlated with disease activity,indicating that IL-35 may be a potential marker for evaluating the activity of RA.