Circulating microRNAs as potential biomarkers of disease activity and structural damage in ankylosing spondylitis patients

• Published in: Human molecular genetics 2018-03, Vol.27 (5), p.875-890
• Main Authors: Perez-Sanchez, Carlos, Font-Ugalde, Pilar, Ruiz-Limon, Patricia, Lopez-Pedrera, Chary, Castro-Villegas, Maria C, Abalos-Aguilera, Maria C, Barbarroja, Nuria, Arias-de la Rosa, Ivan, Lopez-Montilla, Maria D, Escudero-Contreras, Alejandro, Lopez-Medina, Clementina, Collantes-Estevez, Eduardo, Jimenez-Gomez, Yolanda
• Format: Article
• Language: English
• Subjects: Adult; Biomarkers - blood; Case-Control Studies; Circulating MicroRNA - blood; Circulating MicroRNA - metabolism; Female; Gene Expression Profiling; Humans; Interleukin-5 - blood; Male; MicroRNAs - blood; Middle Aged; Spondylitis, Ankylosing - blood; Spondylitis, Ankylosing - diagnosis; Spondylitis, Ankylosing - genetics; Tumor Necrosis Factor-alpha - blood
• ISSN: 0964-6906; 1460-2083
• DOI: 10.1093/hmg/ddy008

Abstract Ankylosing spondylitis (AS) remains difficult to diagnose before irreversible damage to sacroiliac joint is noticeable. Circulating microRNAs have demonstrated to serve as diagnostic tools for several human diseases. Here, we analysed plasma microRNAs to identify potential AS biomarkers. Higher expression levels of microRNA (miR)-146a-5p, miR-125a-5p, miR-151a-3p and miR-22-3p, and lower expression of miR-150-5p, and miR-451a were found in AS versus healthy donors. Interestingly, higher miR-146a-5p, miR-125a-5p, miR-151a-3p, miR-22-3p and miR-451a expression was also observed in AS than psoriatic arthritis patients. The areas under the curve, generated to assess the accuracy of microRNAs as diagnostic biomarkers for AS, ranged from 0.614 to 0.781; the six-microRNA signature reached 0.957. Bioinformatics analysis revealed that microRNAs targeted inflammatory and bone remodeling genes, underlying their potential role in this pathology. Indeed, additional studies revealed an association between these six microRNAs and potential target proteins related to AS pathophysiology. Furthermore, miR-146a-5p, miR-125a-5p and miR-22-3p expression was increased in active versus non-active patients. Moreover, miR-125a-5p, miR-151a-3p, miR-150-5p and miR-451a expression was related to the presence of syndesmophytes in AS patients. Overall, this study identified a six-plasma microRNA signature that could be attractive candidates as non-invasive biomarkers for the AS diagnosis, and may help to elucidate the disease pathogenesis.