Filková Mária, Aradi Borbala, Senolt Ladislav, Ospelt Caroline, Vettori Serena, Mann Heřman, Filer Andrew, Raza Karim, Buckley Christopher D, Snow Martyn, Vencovský Jiří, Pavelka Karel, Michel Beat A, Gay Renate E, Gay Steffen, Jüngel Astrid
Centre of Experimental Rheumatology, University Hospital Zurich, Zurich, Switzerland.
Department of Clinical and Experimental Rheumatology of the 1st Faculty of Medicine, Institute of Rheumatology, Charles University in Prague, Prague, Czech Republic.
Ann Rheum Dis. 2014 Oct;73(10):1898-904. doi: 10.1136/annrheumdis-2012-202815. Epub 2013 Jul 29.
Identification of parameters for early diagnosis and treatment response would be beneficial for patients with early rheumatoid arthritis (ERA) to prevent ongoing joint damage. miRNAs have features of potential biomarkers, and an altered expression of miRNAs was shown in established rheumatoid arthritis (RA).
To analyse RA associated miRNAs in the sera of patients with ERA to find markers of early disease, clinical activity or predictors of disease outcome.
Total RNA was isolated from whole sera in ERA patients (prior to and after 3 and 12 months of therapy with disease modifying antirheumatic drugs), in patients with established RA and in healthy controls (HC) using phenol-chloroform extraction. Expression of miR-146a, miR-155, miR-223, miR-16, miR-203, miR-132 and miR-124a was analysed by TaqMan Real Time PCR.
From all analysed miRNAs, levels of miR-146a, miR-155 and miR-16 were decreased in the sera of ERA patients in comparison with established RA. A change in circulating miR-16 in the first 3 months of therapy was associated with a decrease in DAS28 in long term follow-up in ERA (p=0.002). Levels of circulating miR-223 in treatment naïve ERA correlated with C reactive protein (p=0.008), DAS28 (p=0.031) and change in DAS28 after 3 months (p=0.003) and 12 months (p=0.011) of follow-up. However, neither miR-16 nor miR-223 could distinguish ERA from HC.
Differential expression of circulating miR-146a, miR-155 and miR-16 in the sera of ERA patients may characterise an early stage of the disease. We suggest miR-223 as a marker of disease activity and miR-16 and miR-223 as possible predictors for disease outcome in ERA.
确定早期诊断和治疗反应的参数将有助于早期类风湿关节炎（ERA）患者预防持续的关节损伤。微小RNA（miRNA）具有作为潜在生物标志物的特征，并且在已确诊的类风湿关节炎（RA）中显示miRNA表达发生改变。
分析ERA患者血清中与RA相关的miRNA，以寻找早期疾病、临床活动或疾病转归的预测指标。
采用酚-氯仿提取法，从ERA患者（使用改善病情抗风湿药物治疗3个月和12个月之前及之后）、已确诊RA患者和健康对照（HC）的全血清中分离总RNA。通过TaqMan实时荧光定量PCR分析miR-146a、miR-155、miR-223、miR-16、miR-203、miR-132和miR-124a的表达。
在所有分析的miRNA中，与已确诊RA相比，ERA患者血清中miR-146a、miR-155和miR-16的水平降低。治疗前3个月循环miR-16的变化与ERA长期随访中疾病活动度评分（DAS28）的降低相关（p=0.002）。未经治疗的ERA患者循环miR-223水平与C反应蛋白（p=0.008）、DAS28（p=0.031）以及随访3个月（p=0.003）和12个月（p=0.011）后DAS28的变化相关。然而，miR-16和miR-223均无法区分ERA患者与HC。
ERA患者血清中循环miR-146a、miR-155和miR-16的差异表达可能是疾病早期阶段的特征。我们建议将miR-223作为疾病活动的标志物，将miR-16和miR-223作为ERA疾病转归的可能预测指标。
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