Circulatory microRNA signature distinguishing rheumatoid arthritis and psoriatic arthritis

OBJECTIVES: Gene regulatory microRNA (miRNA) have emerged as promising biomarkers and therapeutic targets in autoimmunity pathology. This study examines circulatory miRNA as cellular biomarkers that can distinguish rheumatoid arthritis (RA) from psoriatic arthritis (PsA) to evaluate the potential implications for disease pathogenesis. METHODS: RA (n = 48) and PsA (n = 50) patients and healthy controls (HC) (n = 20) were recruited and serums obtained. Multiplex analysis of serum miRNAs was performed using the FirePlex miRNA Immunology-V2 panel (FirePlex Bioworks Inc.). DNA intelligent analysis (DIANA)-mirPath and STRING software were used to predict pathways targeted by the dysregulated miRNAs. RESULTS: 7 miRNAs; miR-126-3p, miR-29b-3p, miR-22-3p, miR-223-3p, miR-320a, let-7e-5p, and let-7g-5p were significantly elevated in RA serum compared with PsA (all p< 0.05), in addition to HC (all p< 0.05), with high sensitivity and specificity as determined by receiver-operating characteristic curve analysis. PCA and biplot analysis demonstrated differential miRNA clustering between both disease states with a dominant skew towards 3 specific miRNA in RA vs PsA; miR-29b-3p, miR-22-3p, and miR-223-3p. DIANA analysis and STRING visualisation of this miRNA signature identified downstream target pathways including PI3K-Akt and FoxO signalling, all importantly associated with aspects of RA pathogenesis including angiogenesis, invasion, and cell death. CONCLUSION: This study identified three key miRNAs demonstrating differential expression levels between RA and PsA, which potentially govern downstream inflammatory pathways regulating distinct disease mechanisms. Therefore, 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.