Abstract

ObjectivesDysregulation of miRNAs and their target genes contributes to the pathophysiology of autoimmune diseases. Circulating miRNAs may serve as diagnostic/prognostic biomarkers. We aimed to investigate the association between circulating miRNAs, disease activity and spinal involvement in patients with axial spondyloarthritis (AxSpA).MethodsTotal RNA was isolated from the plasma of patients with non-radiographic (nr)AxSpA, patients with ankylosing spondylitis (AS) and healthy controls (HC) via phenol-chloroform extraction. A total of 760 miRNAs were analysed with TaqMan® Low Density Arrays, and the expression of 21 miRNAs was assessed using single assays.ResultsComprehensive analysis demonstrated the differential expression of miRNAs among patients with progressive spinal disease. Of the 21 miRNAs selected according to their expression patterns, the levels of miR-625-3p were significantly different between nr-AxSpA patients and HCs. We found no correlation between miRNA levels and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in nr-AxSpA patients. Selected miRNAs, such as miR-29a-3p, miR-146a-5p or miR-222-3p with an established role in extracellular matrix formation and inflammation were associated with spinal changes and/or disease activity assessed by BASDAI in AS patients, including miR-625-3p reflecting disease activity in AS with spinal involvement.ConclusionsOur data indicate that circulating miRNAs play a role in the pathogenesis of AxSpA and are also suggestive of their potential as biomarkers of disease progression. We hypothesize that differential systemic levels of miRNA expression reflect miRNA dysregulation at sites of spinal inflammation or bone formation where these molecules contribute to the development of pathophysiological features typical of AxSpA.

Highlights

  • Axial spondyloarthritis (AxSpA) is a chronic inflammatory disease that mainly affects the axial skeleton, sacroiliac joints and entheseal spinal structures

  • Of the 21 miRNAs selected according to their expression patterns, the levels of miR-625-3p were significantly different between nr-axial spondyloarthritis (AxSpA) patients and healthy controls (HC)

  • We found no correlation between miRNA levels and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in nr-AxSpA patients

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Summary

Introduction

Axial spondyloarthritis (AxSpA) is a chronic inflammatory disease that mainly affects the axial skeleton, sacroiliac joints and entheseal spinal structures. It encompasses patients with ankylosing spondylitis (AS) with radiographic sacroiliitis and syndesmophytes, as well as patients with early or abortive forms of spondyloarthritis (SpA) characterized by the presence of sacroiliac inflammation detected by magnetic resonance imaging (MRI) or the presence of HLA-B27 in combination with features characteristic of SpA [1, 2]. AS is an inflammatory disease characterized by new bone formation. Patients may have longstanding symptoms, the diagnosis of AS based on the modified New York criteria delays early treatment, as radiographic sacroiliitis represents a late sign of disease. Early diagnosis, disease monitoring and therapeutic response prediction are very important

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