微小RNA-125b：与早期类风湿关节炎患者疾病活动度及治疗反应的关联
MicroRNA-125b: association with disease activity and the treatment response of patients with early rheumatoid arthritis.
作者信息
Hruskova Veronika, Jandova Romana, Vernerova Lucia, Mann Herman, Pecha Ondrej, Prajzlerova Klara, Pavelka Karel, Vencovsky Jiri, Filkova Maria, Senolt Ladislav
机构信息
Institute of Rheumatology and Department of Rheumatology, First Faculty of Medicine, Charles University in Prague, Na Slupi 4, 12850, Prague 2, Czech Republic.
Faculty of Science Charles University in Prague, Prague, Czech Republic.
出版信息
Arthritis Res Ther. 2016 Jun 2;18(1):124. doi: 10.1186/s13075-016-1023-0.
BACKGROUND
MicroRNAs (miRNAs) are small RNAs that regulate gene expression by targeting mRNA. It was proved that some miRNAs are significantly deregulated in rheumatoid arthritis (RA). MicroRNA-125b negatively regulates expression of TNF-α, which plays a crucial role in RA pathogenesis. The aim of this study was to determine the treatment outcome of patients with early RA based on the expression of circulating and cellular miR-125b.
METHODS
Total RNA was isolated from the plasma and peripheral blood mononuclear cells (PBMCs) of 58 patients with early RA before and three months after treatment initiation and of 54 age- and sex-matched healthy controls (HC). The expression of miR-125b was measured by TaqMan quantitative PCR. The treatment responders were defined as patients achieving remission or low disease activity (28-joint count disease activity score (DAS28) <3.2). Receiver operating characteristic (ROC) curve and stepwise backward multivariable logistic regression analyses of miR-125b expression were used to predict the disease outcome at three and six months after initiation of treatment.
RESULTS
The expression of miR-125b in the PBMCs and plasma of treatment-naïve early RA patients was significantly lower than that of HC and increased significantly after three months of treatment, particularly in responders. However, only the cellular expression of miR-125b was inversely correlated with disease activity. MiR-125b expression in PBMCs was higher in responders than in non-responders after three months (p = 0.042). Using ROC analysis, the cellular expression of miR-125b, but not the disease activity at baseline, predicted the treatment response after three months of therapy (area under the curve 0.652 (95 % CI 0.510 to 0.793); p = 0.048).
CONCLUSION
The expression of miR-125b in PBMCs of treatment-naïve patients may present a novel biomarker for monitoring the treatment outcome during the early phase of RA.
背景
微小RNA（miRNA）是一类通过靶向mRNA来调节基因表达的小RNA。已证实某些miRNA在类风湿关节炎（RA）中显著失调。微小RNA-125b负向调节肿瘤坏死因子-α（TNF-α）的表达，而TNF-α在RA发病机制中起关键作用。本研究的目的是基于循环和细胞中miR-125b的表达来确定早期RA患者的治疗结果。
方法
从58例早期RA患者治疗开始前及治疗三个月后的血浆和外周血单个核细胞（PBMC）以及54例年龄和性别匹配的健康对照（HC）中分离总RNA。通过TaqMan定量PCR检测miR-125b的表达。治疗反应者定义为达到缓解或低疾病活动度（28关节计数疾病活动评分（DAS28）<3.2）的患者。采用miR-125b表达的受试者工作特征（ROC）曲线和逐步向后多变量逻辑回归分析来预测治疗开始后三个月和六个月的疾病结果。
结果
未经治疗的早期RA患者PBMC和血浆中miR-125b的表达显著低于HC，治疗三个月后显著增加，尤其是反应者。然而，只有细胞中miR-125b的表达与疾病活动度呈负相关。三个月后，反应者PBMC中miR-125b的表达高于无反应者（p = 0.042）。使用ROC分析，miR-125b的细胞表达而非基线时的疾病活动度可预测治疗三个月后的治疗反应（曲线下面积0.652（95%CI 0.510至0.79）；p = 0.048）。
结论
未经治疗患者PBMC中miR-125b的表达可能是监测RA早期治疗结果的一种新型生物标志物。
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