Distinct Circulating microRNA Signature Differentiates RA From Psoriatic Arthritis
Key Clinical Summary
- A serum-based analysis identified seven circulating microRNAs that were significantly elevated in rheumatoid arthritis (RA) compared with psoriatic arthritis (PsA) and healthy controls, supporting their potential as noninvasive diagnostic biomarkers.
- Receiver operating characteristic analyses demonstrated high sensitivity and specificity for distinguishing RA from PsA, while principal component analyses showed clear separation between the two diseases.
- Bioinformatic pathway analyses linked differentially expressed miRNAs to PI3K-AKT and FoxO signaling pathways, suggesting biologic mechanisms that may contribute to disease-specific inflammatory processes.
Rheumatoid arthritis and psoriatic arthritis often share overlapping clinical features, making early diagnostic discrimination challenging. In a serum-based biomarker analysis, investigators identified a distinct circulating microRNA (miRNA) signature that differentiated RA from PsA and healthy controls, supporting the potential role of noninvasive biomarkers in improving diagnosis while providing insight into disease-specific inflammatory mechanisms.
Study Findings
Investigators analyzed serum samples from 48 patients with RA, 49 patients with PsA, and 20 healthy controls using the FirePlex miRNA Immunology-V2 panel. Differentially expressed circulating miRNAs were subsequently evaluated using pathway prediction software to identify biologic processes associated with the observed expression patterns.
Seven circulating miRNAs were significantly elevated in patients with RA compared with both PsA and healthy controls (all P < .05): miR-126-3p, miR-29b-3p, miR-22-3p, miR-223-3p, miR-320a, let-7e-5p, and let-7g-5p.
Receiver operating characteristic (ROC) curve analysis demonstrated high sensitivity and specificity for distinguishing RA from PsA based on the identified miRNA profile. In addition, principal component and biplot analyses showed distinct clustering between the two diseases, indicating that circulating miRNA expression patterns differed substantially between RA and PsA.
According to the investigators, "there was a dominant skew towards three specific miRNAs in RA vs PsA: miR-29b-3p, miR-22-3p and miR-223-3p." These 3 miRNAs appeared to contribute substantially to the separation observed between disease groups.
Bioinformatic analyses further suggested that the differentially expressed miRNAs regulate signaling pathways implicated in RA pathogenesis. DIANA-mirPath and STRING analyses identified downstream targets involving phosphoinositide 3-kinase (PI3K)-AKT and FoxO signaling pathways, both of which are associated with angiogenesis, tissue invasion, and cell death.
Clinical Implications
Accurately distinguishing RA from PsA remains clinically important because the 2 inflammatory arthritides can present with overlapping symptoms despite differences in underlying disease mechanisms and treatment approaches. The identification of a circulating serum miRNA signature may offer a noninvasive strategy to improve diagnostic discrimination.
Beyond diagnostic performance, the observed differences in miRNA expression may provide insight into disease-specific biology. The association between the identified miRNAs and PI3K-AKT and FoxO signaling pathways suggests that these biomarkers may reflect inflammatory processes relevant to RA pathogenesis.
The findings also highlight the potential utility of integrating molecular biomarkers with clinical assessment to better characterize inflammatory arthritis. However, the study evaluated a relatively modest cohort, and the findings should be interpreted within the context of this serum-based analysis.
Expert Commentary
The investigators concluded "circulating miRNAs may be valuable as non-invasive diagnostic biomarkers that can distinguish RA from PsA and may additionally assist in elucidating differential disease pathogenesis."
These findings support further investigation of circulating miRNAs as noninvasive diagnostic biomarkers and as tools for improving understanding of disease-specific inflammatory mechanisms.
Reference
Órla Tynan, Megan M Hanlon, Achilleas Floudas, Siobhán Wade, Ursula Fearon, Douglas J Veale. Circulatory microRNA signature distinguishing rheumatoid arthritis and psoriatic arthritis. Rheumatology, Volume 65, Issue 6. https://doi.org/10.1093/rheumatology/keag246
