Background and objectives The altered expression of miRNAs and dysregulation of their target genes has been shown to contribute to pathophysiology of many autoimmune diseases. In addition, circulating miRNAs may serve as diagnostic and/or prognostic biomarkers. Our aim was to identify circulating miRNAs in patients with axial spondyloarthritis (AxSpA) and to investigate their relationship with spinal involvement and disease activity.
Material and methods Total RNA was isolated using phenol-chloroform extraction from plasma of 20 patients with non-radiographic AxSpA (nr-AxSpA), 48 patients with radiographic AxSpA (with and without spinal involvement, including 6 patients with a bamboo spine), and 29 healthy controls (HC). A comprehensive analysis of miRNAs was performed using TaqMan® Low Density Array (TLDA) in 5 samples from each group. Expression of miRNAs was further confirmed by single assays in the remaining samples and the levels were normalised to C. elegans spike-in controls. Disease activity was assessed based on C-reactive protein (CRP) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Data were analysed using one-way ANOVA, unpaired t-test with Welch’s correction and Pearson correlation.
Results Out of 760 miRNAs analysed by TLDA, 21 miRNAs were selected for further analysis, according to differences in the expression and role in the inflammation and bone metabolism. Fourteen miRNAs were significantly lower (p < 0.05) in all patients with AxSpA compared to HC. In all patients with radiographic AxSpA (r-AxSpA), 20 miRNAs were significantly lower in comparison with the group of nr-AxSpA patients and HC, in particular miR-24, miR-27a, miR-106a or miR-223 (p < 0.0001). Levels of these miRNAs were significantly lower (p < 0.05) in a subgroup of patients with bamboo spine compared with other patients with AxSpA. We found, that e.g. miR-625* and miR-885–5p significantly correlated with BASDAI in all patients with r-AxSpA (r = 0.330; p = 0.043 and r = 0.433; p = 0.007 respectively) and were more pronounced in patients with spinal involvement (r = 0.570; p = 0.011 and r = 0.587; p = 0.008). Furthermore, miR-29a significantly correlated with BASDAI (r = 0.474; p = 0.040) and CRP (r = 0.625; p = 0.004) in patients with spinal involvement.
Conclusions Our analysis revealed different expression of several circulating miRNAs associated with the degree of spinal involvement and disease activity. Our data suggest role of these miRNA in the pathogenesis of AxSpA and potential use of circulating miRNAs as biomarkers of disease progression.
Acknowledgements IGA project no. NT 14498, project of MHCR for conceptual development of research organisation 023728 and SVV 260 031.