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Open AccessArticle

Synovial-Fluid miRNA Signature for Diagnosis of Juvenile Idiopathic Arthritis

1
IRMB, INSERM, Univ. Montpellier, F-34000 Montpellier, France
2
Arthritis R&D, F-92200 Neuilly sur Seine, France
3
Pediatric Department, CHU Montpellier, Univ. Montpellier, F-34000 Montpellier, France
4
Pathogenesis and Control of Chronic Infections, CHU Montpellier, Univ. Montpellier, INSERM, F-34000 Montpellier, France
5
Pediatric Orthopedic Surgery Unit, CHU Montpellier, Univ. Montpellier, F-34000 Montpellier, France
6
Centre d’Investigation Clinique, CHU Montpellier, F-34000 Montpellier, France
7
Centre d’Investigation Clinique 411, INSERM, F-34000 Montpellier, France
8
FIRALIS SA, F-68330 Huningue, France
9
IRCM, INSERM, Univ. Montpellier, ICM, F-34000 Montpellier, France
10
Clinical Department for Osteoarticular Diseases, CHU Montpellier, Univ. Montpellier, F-34000 Montpellier, France
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cells 2019, 8(12), 1521; https://doi.org/10.3390/cells8121521
Received: 6 September 2019 / Revised: 15 November 2019 / Accepted: 21 November 2019 / Published: 26 November 2019
(This article belongs to the Special Issue microRNA as Biomarker)
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. View Full-Text
Keywords: miRNA; juvenile arthritis; biomarker; synovial fluid miRNA; juvenile arthritis; biomarker; synovial fluid
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Nziza, N.; Jeziorski, E.; Delpont, M.; Cren, M.; Chevassus, H.; Carbasse, A.; Mahe, P.; Abassi, H.; Joly-Monrigal, P.; Schordan, E.; Mangé, A.; Jorgensen, C.; Apparailly, F.; Duroux-Richard, I. Synovial-Fluid miRNA Signature for Diagnosis of Juvenile Idiopathic Arthritis. Cells 2019, 8, 1521.

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