Background/Purpose: MicroRNAs (miRNAs) modulate gene expression by inhibiting the translation of targeted mRNAs and causing mRNA degradation in a transcript-specific manner. Several miRNAs have been reported to play an important role in inflammation and autoimmune diseases. Our aim was to identify miRNA biomarkers in oligoarticular juvenile idiopathic arthritis (JIA).

Methods: Total RNA was isolated and microarray profiling on 84 inflammatory miRNAs was performed to identify differentially expressed miRNAs on pooled (n=5) healthy plasma, JIA plasma and synovial fluid (SF) by digital droplet PCR (DDPCR) that enables absolute quantification of nucleic acids. Levels of four candidate miRNAs; miR-125b, miR-146b, miR-155 and miRNA-192-5p in plasma and SF were quantified by DDPCR individually in additional 10 healthy controls and 10 age and gender matched oligoarticular JIA patients. All patients satisfied the ILAR classification criteria, were all ANA positive and non- or only NSAID treated at the time of joint injection when also the blood was collected.

Results:  We identified 11 and 13 miRNAs on the microarray analysis that were at least 2-fold increased or decreased in JIA plasma compared to normal plasma, and in JIA SF compared to JIA plasma, respectively. The differential expression of miR-146b, miR-155 and miR-192-5p were confirmed on individual samples. Levels of miR-146b and miR-155 was increased in plasma (p=0.03 and p=0.01 respectively) of JIA patients and miR-146b was enriched even more at the site of the inflamed joints (p=0.02). MiRNA-192-5p expression was reduced in arthritic joints (p=0.003). MiRNA-125b expression did not show any significant difference.

Conclusion: This is the first study to investigate miRNAs by DDPCR in JIA and especially in SF. Similar to what is known in rheumatoid arthritis, miRNA-146b and miRNA-155 may promote an inflammatory process in oligoarticular JIA. Our novel finding is that miRNA192-5p is down-regulated in JIA in the inflamed joint. This may be involved in suppressing proinflammatory signals. Investigation of miRNAs and exploring their potential biological functions could help to understand the pathogenesis of JIA. The inflammation regulating miRNAs may have the potential to serve as biomarkers of disease or novel therapeutic targets.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/inflammation-regulating-micrornas-mir-146b-mir-155-and-mir-192-5p-are-altered-in-plasma-and-synovial-fluid-of-oligoarticular-juvenile-idiopathic-arthritis/