4.6 Article

Synovial-Fluid miRNA Signature for Diagnosis of Juvenile Idiopathic Arthritis

期刊

CELLS
卷 8, 期 12, 页码 -

出版社

MDPI
DOI: 10.3390/cells8121521

关键词

miRNA; juvenile arthritis; biomarker; synovial fluid

资金

  1. INSERM (Institut National de la Sante et Recherche Medicale)
  2. University of Montpellier
  3. Arthritis Fondation Courtin
  4. Arthritis RD [2015/1454]
  5. SPILF grant
  6. Montpellier University Hospital Centre [AOI 466 ARTEMIS UF9361-2]
  7. Fondation de l'Avenir [AP-RMA-16-033]

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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 K. kingae 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.

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