Session Title: Genetics, Genomics and Proteomics
Session Type: Abstract Submissions (ACR)
The altered expression of miRNAs and dysregulation of their target genes has been shown to contribute to the development and maintenance of autoimmune diseases. In addition, cell-free circulating miRNAs appear promising 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.
The study included 20 patients with non-radiographic AxSpA (nr-AxSpA) according to the ASAS criteria with sacroiliitis confirmed by MRI, 48 patients with radiographic AxSpA (with and without spinal involvement, including 5 patients with a bamboo spine), and 29 healthy controls (HC). Total RNA from plasma was isolated using phenol-chloroform extraction and equal amount of RNA was used for reverse transcription. A comprehensive analysis of miRNAs was performed using TaqMan® Low Density Array (TLDA) in 5 samples from each group. dCt method was used for relative quantification as follows: dCt= Ct(array average)-Ct(miRNA) followed by x-fold change calculation. The expression of selected miRNAs was further validated by single assays in the remaining samples and the levels of miRNAs were normalized to an average of 3 spike-in controls of C. elegans origin: dCt= Ct(spike-in average)-Ct(miRNA). Data were analyzed using one-way ANOVA and unpaired t-test with Welch’s correction.
Out of total 760 miRNAs analysed by TLDA, 162 miRNAs were detected in a group of HC, 156 miRNAs in patients with nr-AxSpA and 110 in patients with radiographic AxSpA. All patients with AxSpA had at least 2-fold lower levels of 56 miRNAs when compared with HC. In patients with radiographic AxSpA, 72 miRNAs showed at least 2-fold decrease in comparison with nr-AxSpA.
Twenty-one miRNAs were selected according to the differential expression between groups of patients and possible relationship to the pathogenesis of AxSpA for further analysis. Out of 21 selected miRNAs, 14 miRNAs were significantly lower (p<0.05) in all patients with AxSpA compared to HC. MiR-625* (p=0.0055) and miR-222 (p=0.045) showed significantly lower levels in patients with nr-AxSpA compared with HC. In all patients with radiographic 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, miR-222 or miR-223 (p<0.0001). Levels of these miRNAs were significantly lower (p<0.01 for miR-24, -27a, -106a, -223, p<0.05 for miR-222) in a subgroup of patients with bamboo spine compared with other patients with AxSpA.
Expression of circulating miRNAs is altered in patients with AxSpA. Reduced expression of several miRNAs was associated with the degree of spinal involvement, with the lowest expression observed in patients with the bamboo spine. Given the involvement of these dysregulated miRNAs in innate immunity and new bone formation, our data suggest their role in the pathogenesis of AxSpA and potential use of circulating miRNAs as biomarkers of disease progression.
IGA project no. NT 14498, project of MHCR for conceptual development of research organization 023728, IMI BTCure, Osteoimmune.
MHCR project 023728,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/association-of-circulating-mirnas-with-spinal-involvement-in-patients-with-axial-spondyloarthritis/