RNA Biomarkers in Synovial Fluid Can Accurately Identify JIA, Study Suggests

RNA Biomarkers in Synovial Fluid Can Accurately Identify JIA, Study Suggests
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Researchers have identified three diagnostic biomarkers of juvenile idiopathic arthritis (JIA) in synovial fluid — the liquid between certain joints — which may help to distinguish the condition from septic arthritis (SA) in children.

These biomarkers could also advance understanding of JIA’s underlying mechanisms and reveal new targets for potential treatments, the investigators said.

Their study, “Synovial-Fluid miRNA Signature for Diagnosis of Juvenile Idiopathic Arthritis,” was published in the journal Cells.

MicroRNAs, or miRNAs, are small RNA molecules that target a specific gene’s messenger RNA (mRNA) — derived from DNA and used as a template for protein production — to prevent generation of that protein. Given their specificity, stability, and detectable presence in body fluids, miRNAs have been proposed as biomarkers for several diseases.

Altered levels of miRNAs have been associated with disorders such as rheumatoid arthritis (RA). Previous research has identified a pattern of miRNAs in the synovial fluid of adults with RA and showed that such potential biomarkers could specifically detect the disorder.

However, the potential role of miRNAs as biomarkers in JIA remains largely unexplored.

“Identifying specific biomarkers is essential to help characterize and classify JIA diseases for early diagnosis and proposing molecules related to specific [disease-associated mechanisms] for future therapeutic innovation,” the researchers wrote.

In addition, biomarkers are also needed to distinguish between JIA and SA (or infectious arthritis), another type of arthritis that mainly affects children.

In the study, researchers in France have identified for the first time a miRNA signature in synovial fluid, which contains three miRNAs that, when combined, can efficiently differentiate JIA from SA.

They first analyzed the levels of 2,084 miRNAs in the blood and synovial fluid of five children with JIA (mean age of 10.3 years) and three children with SA (1.2 years). Then, the results were validated in two independent groups of patients comprising 26 children (13 with JIA and 13 with SA).

Of note, SA in these children was caused by a bacterial infection with Kingella kingae, the most common cause of the disease.

Results showed that 198 blood miRNAs (10%) and 419 synovial fluid miRNAs (more than 20%) had significantly different levels between the two diseases.

Additional analysis with stricter thresholds identified 141 miRNAs with significantly different levels between the two diseases in the synovial fluid, but none in the blood. This showed that, compared to those in blood, synovial fluid miRNAs could better differentiate JIA from SA, suggesting “specific disease-related changes in miRNA [levels] within inflamed joints,” the team added.

Using even stricter parameters, the scientists reduced the list to 21 synovial fluid miRNAs that were produced differently between children with JIA and those with SA. Nineteen of these miRNAs were validated in the two additional independent groups of patients.

In particular, the combined detection of three synovial fluid miRNAs — miR-6764-5p, miR-155, and miR-146a-5p — was sufficient to efficiently discriminate JIA from SA in children.

Further analysis revealed that these 19 miRNAs were involved in a number of key biological processes, including those associated with insulin, heart cells, the immune B-cell receptor, and the EGF/EGFR signaling pathways (involved in immune responses). Interestingly, abnormalities in these processes had been previously associated with JIA.

Previous research has suggested that these miRNAs are associated with autoimmune rather than infectious processes, which reflect the respective cause of each disease, the researchers said.

“We propose, for the first time, a synovial fluid-specific miRNA signature for JIA … [that] may indicate potential biomarkers to assist in the classification and differential diagnosis of JIA” and help in understanding its underlying mechanisms, the researchers wrote.

However, larger studies that evaluate the levels of proteins involved in the identified processes are required to confirm these findings, they added.

Marta Figueiredo holds a BSc in Biology and a MSc in Evolutionary and Developmental Biology from the University of Lisbon, Portugal. She is currently finishing her PhD in Biomedical Sciences at the University of Lisbon, where she focused her research on the role of several signalling pathways in thymus and parathyroid glands embryonic development.
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José holds a PhD in Neuroscience from Universidade of Porto, in Portugal. He has also studied Biochemistry at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario in London, Ontario, Canada. His work has ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimer’s disease.

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Marta Figueiredo holds a BSc in Biology and a MSc in Evolutionary and Developmental Biology from the University of Lisbon, Portugal. She is currently finishing her PhD in Biomedical Sciences at the University of Lisbon, where she focused her research on the role of several signalling pathways in thymus and parathyroid glands embryonic development.
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