血清和尿液中miR-16、miR-146a和miR-155在幼年特发性关节炎诊断和监测中的应用。
The utility of miR-16, miR-146a and miR-155 in serum and urine for juvenile idiopathic arthritis diagnostics and monitoring.
作者信息
Snipaitiene Ausra, Snipaitiene Kristina, Slegeryte Andzelika, Buragaite-Staponkiene Benita, Baranauskaite Asta, Jarmalaite Sonata, Jankauskaite Lina
机构信息
Faculty of Medicine, Pediatric Department, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Institute of Biosciences, Life Sciences Center, Vilnius University, Vilnius, Lithuania.
出版信息
Pediatr Rheumatol Online J. 2025 Jul 28;23(1):79. doi: 10.1186/s12969-025-01136-w.
BACKGROUND
Biomarker search for juvenile idiopathic arthritis (JIA) diagnosis and monitoring remain the focus of research worldwide. Several microRNAs (miRNAs) have been identified as relevant in different rheumatic conditions; however, studies in JIA remain limited. Our study aimed to explore the potential of serum and urine-derived miRNAs for JIA diagnostics and longitudinal JIA monitoring.
METHODS
In this single-center, prospective study, three selected miRNAs (miR-16, -146a and -155) were tested in serial serum and urine samples collected from 31 JIA patients and 22 healthy controls (HC) via quantitative reverse transcription polymerase chain reaction (RT‒qPCR). The diagnostic performance of variables for distinguishing JIA patients from HCs was assessed by determining the area under the receiver operating characteristic (ROC) curve (AUC). The prediction of remission was evaluated using Cox regression and Kaplan-Meier analyses. A p-value < 0.05 was considered statistically significant.
RESULTS
Lower miR-16 and higher miR-155 levels were detected in serum of JIA patients' vs. HC (p < 0.01), whereas the level of miR-146a was lower in urine of JIA patients (p = 0.032). In ROC analysis, miR-16 and miR-155 distinguished JIA patients from HC when analyzed in serum (AUC 0.81, 95% CI 0.70-0.93, p < 0.001 and AUC 0.73, 95% CI 0.59-0.87, p = 0.005, respectively), and miR-146a- in urine (AUC 0.68, 95% CI 0.53-0.82, p = 0.030). During 12 months follow-up period increasing miR-16 (p = 0.021) and decreasing miR-155 (p = 0.009) levels were observed in serum samples. Kaplan-Meier survival analysis revealed that a high level of miR-146a in serum significantly predicts JIA remission (HR = 2.2, 95% CI 0.7-6.9, p = 0.040).
CONCLUSIONS
This study highlights the utility of miRNAs in JIA diagnosis, monitoring and prognosis and demonstrates the feasibility of using urine as a noninvasive source of miRNAs in children with non-systemic JIA.
背景
寻找用于青少年特发性关节炎（JIA）诊断和监测的生物标志物仍是全球研究的重点。几种微小RNA（miRNA）已被确定与不同的风湿性疾病相关；然而，关于JIA的研究仍然有限。我们的研究旨在探索血清和尿液来源的miRNA在JIA诊断及JIA纵向监测中的潜力。
方法
在这项单中心前瞻性研究中，通过定量逆转录聚合酶链反应（RT-qPCR）对从31例JIA患者和22名健康对照（HC）收集的系列血清和尿液样本中的三种选定miRNA（miR-16、-146a和-155）进行检测。通过确定受试者工作特征（ROC）曲线下面积（AUC）来评估区分JIA患者和HC的变量的诊断性能。使用Cox回归和Kaplan-Meier分析评估缓解的预测情况。p值<0.05被认为具有统计学意义。
结果
与HC相比，JIA患者血清中检测到较低的miR-16水平和较高的miR-155水平（p<0.01），而JIA患者尿液中miR-146a水平较低（p=0.032）。在ROC分析中，当在血清中分析时，miR-16和miR-155可区分JIA患者和HC（AUC分别为0.81，95%CI 0.70-0.93，p<0.001和AUC 0.73，95%CI 0.59-0.87，p=0.005），尿液中的miR-146a也可区分（AUC 0.68，95%CI 0.53-0.82，p=0.030）。在12个月的随访期内，血清样本中观察到miR-16水平升高（p=0.021）和miR-155水平降低（p=0.009）。Kaplan-Meier生存分析显示，血清中高水平的miR-146a显著预测JIA缓解（HR=2.2，95%CI 0.7-6.9，p=0.040）。
结论
本研究突出了miRNA在JIA诊断、监测和预后中的作用，并证明了将尿液作为非系统性JIA患儿miRNA无创来源的可行性。
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