Pos0433 relationship between mirna-1-3p, interleukin-17 and tumor necrosis factor in patients with axial spondyloarthritis

Background microRNAs (miRNAs) are small non-coding RNAs that can regulate gene expression and mirror the patient’s health condition. miRNAs deregulation is considered a crucial factor in the development and progression of various diseases, including axial spondyloarthritis (axSpA) [1]. Objectives The aim of the study was to profile the miRNome of peripheral blood mononuclear cells (PBMCs), to identify specific miRNAs and their association with several cytokines, axSpA disease activity and spinal impairment. Methods Massive parallel sequencing (MPS, Ilumina) was performed for miRNAs profiling in 96 subjects (38 patients with non-radiographic (nr-) axSpA, 38 patients with radiographic (r-) axSpA and 20 healthy controls (HC)). The expression of candidate miRNAs was validated using the qRT-PCR system (SmartChip) on a new cohort of 47 patients with nr-axSpA, 44 patients with r-axSpA and 50 HC. Disease activity was determined using C-reactive protein (CRP) and Ankylosing Spondylitis Disease Activity Score (ASDAS). Radiographs of the cervical and lumbar spine were assessed by two independent blinded readers using modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). We employed DESeq2 and generalized linear modelling with a negative binomial assumption (GLM-NB) to evaluate the association of candidate miRNAs to the radiographic form, ASDAS and CRP. Linear modelling was used to determine the association between miRNAs and laboratory/clinical parameters adjusted for CRP, age and sex. Results MPS detected 432 miRNAs; however, only 90 miRNAs passed through the selection criteria (p<0.05, BaseMean>10, the difference in log2FC>0.5). We selected 45 miRNAs for validation based on the selection criteria and the literature. We validated miR-1-3p (p=0.006, FC=1.757) to be upregulated and miR-1248 (p=0.002, FC=-1.125) and miR-1246 (p=0.002, FC = -1.125) to be downregulated in patients with axSpA compared to HC. In addition, the expression of miR-1-3p correlated with the plasma levels of IL-17 (p=0.016, τ=0.25) and TNF (p=0.028, τ=0.22), but not with the gene expression of IL-17 or TNF in PBMCs. miR-1-3p (p=0.039, β=0.665) as well as miR-1248 (p<0.001, β=-0.207) correlated with the IL-6 gene expression in PBMCs. None of the miRNAs distinguished between radiographic and non-radiographic disease or correlated with disease activity or radiographic spinal impairment. Conclusion This cross-sectional study failed to demonstrate association between cellular miRNAs, disease activity or spinal impairment, but the association between miR-1-3p, IL-17 and TNF may suggest its role in the pathogenesis of axSpA. Reference [1]Prajzlerová K, Grobelná K, Hušáková M, et al. Association between circulating miRNAs and spinal involvement in patients with axial spondyloarthritis. PLoS One. 2017 Sep 22;12(9):e0185323. Acknowledgements Supported by MHCR No. 023728, BBMRI-CZ LM2018125 and SVV 260 523. Disclosure of Interests None Declared.