IRMB, INSERM, Univ Montpellier, F-34000 Montpellier, France.
Arthritis R&D, F- 92200 Neuilly sur Seine, France.
Cells. 2019 Nov 26;8(12):1521. doi: 10.3390/cells8121521.
Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory rheumatism in childhood; microRNAs (miRNAs) have been proposed as diagnostic biomarkers. Although joints are the primary targets for JIA, a synovial fluid-based miRNA signature has never been studied. We aim to identify miRNA biomarkers in JIA by comparing synovial fluid and serum samples from children with JIA and septic arthritis (SA). With next-generation high-throughput sequencing, we measured the absolute levels of 2083 miRNAs in synovial fluid and serum from an exploratory cohort of children and validated differentially expressed miRNAs in a replication study by using RT-qPCR. We identified a 19-miRNA signature only in synovial fluid samples that was significantly deregulated, with at least 2-fold change in expression, in JIA versus SA (p < 0.01). The combination of miR-6764-5p, miR-155, and miR-146a-5p expression in synovial fluid yielded an area under the receiver operating characteristic curve of 1 (95% CI 0.978 to 1), thereby perfectly differentiating JIA from SA in children. We propose, for the first time, a synovial fluid-specific miRNA signature for JIA and associated signaling pathways that may indicate potential biomarkers to assist in the classification and differential diagnosis of JIA and help in understanding JIA pathogenesis.
幼年特发性关节炎（JIA）是儿童中最常见的慢性炎症性风湿病；microRNAs（miRNAs）已被提议作为诊断生物标志物。尽管关节是 JIA 的主要靶标，但从未研究过基于滑液的 miRNA 特征。我们旨在通过比较 JIA 和脓毒性关节炎（SA）患儿的滑膜液和血清样本，来鉴定 JIA 中的 miRNA 生物标志物。通过下一代高通量测序，我们测量了来自儿童探索性队列的滑膜液和血清中 2083 个 miRNAs 的绝对水平，并通过 RT-qPCR 在复制研究中验证了差异表达的 miRNAs。我们仅在滑膜液样本中发现了一个 19-microRNA 特征，其在 JIA 与 SA 之间的表达明显失调，表达水平至少有 2 倍的变化（p < 0.01）。miR-6764-5p、miR-155 和 miR-146a-5p 在滑膜液中的表达组合得出的受试者工作特征曲线下面积为 1（95%CI 0.978 至 1），从而可以完美地区分儿童中的 JIA 和 SA。我们首次提出了 JIA 及其相关信号通路的滑膜液特异性 miRNA 特征，该特征可能表明潜在的生物标志物，以协助 JIA 的分类和鉴别诊断，并有助于了解 JIA 的发病机制。
