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Synovial-Fluid miRNA Signature for Diagnosis of Juvenile Idiopathic Arthritis
Nadége Nziza1,2, Eric Jeziorski3,4, Marion Delpont5
1IRMB, INSERM, Univ Montpellier, F-34000 Montpellier, France.
Abstract:
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.
Insights
Juvenile idiopathic arthritis (JIA) diagnosis is improved by a novel synovial fluid microRNA (miRNA) signature. This biomarker accurately differentiates JIA from septic arthritis in children, aiding early and precise JIA classification.
Area of Science:
- Pediatric Rheumatology
- Molecular Diagnostics
- Biomarker Discovery
Background:
- Juvenile idiopathic arthritis (JIA) is the most prevalent chronic inflammatory joint disease in children.
- MicroRNAs (miRNAs) are emerging as potential diagnostic biomarkers for various diseases.
- No synovial fluid-based miRNA signature has been established for JIA diagnosis.
Purpose of the Study:
- To identify and validate a synovial fluid-specific miRNA signature for differentiating JIA from septic arthritis (SA) in children.
- To explore the potential of miRNAs as diagnostic biomarkers in pediatric arthritis.
- To investigate signaling pathways associated with the identified miRNA signature in JIA.
Main Methods:
- High-throughput sequencing of 2083 miRNAs in synovial fluid and serum from pediatric JIA and SA patients.
- Validation of differentially expressed miRNAs using RT-qPCR in a separate cohort.
- Statistical analysis including receiver operating characteristic (ROC) curve analysis.
Main Results:
- A 19-miRNA signature was identified exclusively in synovial fluid, significantly deregulated in JIA compared to SA (p < 0.01).
- A combination of miR-6764-5p, miR-155, and miR-146a-5p in synovial fluid achieved a perfect area under the ROC curve (1.0) for differentiating JIA from SA.
- The study proposes novel signaling pathways implicated in JIA pathogenesis based on the miRNA signature.
Conclusions:
- A synovial fluid-specific miRNA signature offers a highly accurate method for distinguishing JIA from SA in children.
- The identified miRNA panel, particularly miR-6764-5p, miR-155, and miR-146a-5p, holds promise as a diagnostic biomarker for JIA.
- This discovery advances the understanding of JIA pathogenesis and aids in differential diagnosis.
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