Department of Pathophysiology and Immunology, National Institute of Geriatrics Rheumatology and Rehabilitation, Warsaw, Poland.
Laboratory of Clinical Immunogenetics and Pharmacogenetics, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
Arch Immunol Ther Exp (Warsz). 2018 Oct;66(5):389-397. doi: 10.1007/s00005-018-0513-y. Epub 2018 May 9.
In this study, we analysed the expression level of sera circulating miRNA-5196 in rheumatoid arthritis (RA) and ankylosing spondylitis (AS) patients before and after tumor necrosis factor (TNF)-α therapy as biomarkers predicting positive treatment outcome. We enrolled 10 RA patients, 13 AS patients, and 12 healthy individuals in the study. The expression of miRNA-5196 was measured by real-time polymerase chain reaction before and after anti-TNF-α therapy. Disease activity of RA patients was assessed using disease activity score 28 (DAS28), whereas ankylosing spondylitis DAS (ASDAS) was used in AS patients. MiRNA-5196 expression was significantly higher in patients with RA and AS before TNF-α therapy than in those following anti-TNF-α therapy and healthy controls. Changes in miRNA-5196 expression positively correlated with delta DAS28 or delta ASDAS, respectively, following TNF-α therapy. In contrast, changes in C-reactive protein (CRP) levels in RA and AS patients did not positively correlate with DAS28 or ASDAS changes. Receiver-operating characteristic analysis showed better diagnostic accuracy of miRNA-5196 expression both in RA (area under curve (AUC) = 0.87, p = 0.055) and AS patients (AUC = 0.90, p = 0.050) compared to CRP levels in RA (AUC = 0.75, p = 0.201) and AS patients (AUC = 0.85, p = 0.086) upon biologic therapy treatment. Finding novel biomarkers, including miRNA-5196 which allow to predict and monitor anti-TNF-α response, would be of clinical value especially during the early phase of RA or AS development.
在这项研究中,我们分析了类风湿关节炎(RA)和强直性脊柱炎(AS)患者在肿瘤坏死因子(TNF)-α治疗前后血清循环 miRNA-5196 的表达水平,作为预测治疗效果的生物标志物。我们纳入了 10 名 RA 患者、13 名 AS 患者和 12 名健康对照者。采用实时聚合酶链反应检测抗 TNF-α治疗前后 miRNA-5196 的表达。RA 患者的疾病活动度采用疾病活动评分 28(DAS28)评估,AS 患者采用强直性脊柱炎疾病活动度评分(ASDAS)。RA 和 AS 患者在 TNF-α治疗前的 miRNA-5196 表达明显高于 TNF-α治疗后的患者和健康对照组。miRNA-5196 表达的变化与 TNF-α治疗后分别的 DAS28 或 ASDAS 的变化呈正相关。相反,RA 和 AS 患者的 C-反应蛋白(CRP)水平的变化与 DAS28 或 ASDAS 的变化无正相关。受试者工作特征曲线分析显示,miRNA-5196 表达在 RA 患者(曲线下面积(AUC)=0.87,p=0.055)和 AS 患者(AUC=0.90,p=0.050)中的诊断准确性优于 RA 患者的 CRP 水平(AUC=0.75,p=0.201)和 AS 患者的 CRP 水平(AUC=0.85,p=0.086)。寻找新的生物标志物,包括 miRNA-5196,可以预测和监测抗 TNF-α反应,在 RA 或 AS 早期发展阶段具有重要的临床价值。