First faculty of medicine, Charles University Prague, Czech Republic
Aneta Pekčcová1, Kristýna Bubová2, Monika Gregova3, Šárka Forejtová2, Jana Hořínková2, Markéta Hušáková2, Michal Tomcik4, Jindřiška Gatterová2, Jiří Vencovský5, Karel Pavelka6, Ladislav Šenolt5 and Jiří Baloun2, 1Institue of Rheumatology, Prague, Prague, Czech Republic, 2Institue of Rheumatology, Prague, Czech Republic, 3Institue of Rheumatology, Prague, 4Institute of Rheumatology, Department of Rheumatology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic, Prague, Czech Republic, 5Institute of Rheumatology and Department of Rheumatology, First Faculty of Medicine, Charles University, Prague, Czech Republic, 6Institute of Rheumatology, Department of Rheumatology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic, Praha, Czech Republic
Background/Purpose: microRNAs (miRNAs) are small non-coding RNAs, which are essential for correct gene expression. The dysregulation in miRNA expression is accompanied by various diseases and may be the cause for the disease development and progression, including axial spondyloarthritis (axSpA) (1).
This study was conducted to profile miRNome of peripheral blood mononuclear cells (PBMCs) and to identify candidate miRNAs determining disease activity in patients with non-radiographic (nr) and radiographic (r) axSpA.
Methods: The miRNome profiling experiment included PBMCs of 96 subjects (38 patients with nr-axSpA, 38 patients with r-axSpA and 20 healthy controls). Firstly, massive parallel sequencing on NextSeq 500 (MPS, Illumina) was performed for miRNA screening. Selected candidate miRNAs were further validated using the qRT-PCR system (SmartChip) on the validation cohort of 47 patients with nr-axSpA, 44 patients with r-axSpA and 50 healthy controls. 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, the disease activity based on ASDAS (The Ankylosing Spondylitis Disease Activity Score) and CRP (C-reactive protein).
Results: We identified 42 differently expressed miRNAs in axSpA patients compared to healthy or in axSpA patients with different disease activity status. In the validation cohort, miR-4286 (p=0.01) expression was higher in patients with very high disease activity than in those with inactive disease (defined by ASDAS). Regression analysis showed a positive association between miR-4286 and the levels of CRP (p=0.047). In addition, miR-1248 (p=0.013) and miR-26a (p=0.027) were downregulated in patients with axSpA compared to healthy controls. miR-451a associated with disease activity (p=0.043) after CRP adjustment.
Conclusion: In this study, we discovered several miRNAs that are associated with disease activity and could play a role in the pathogenesis of axSpA.
Acknowledgement: Supported by MHCR No. 023728, BBMRI-CZ LM2018125 and SVV 260 523.
References: 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.
Disclosures: A. Pekčcová, None; K. Bubová, None; M. Gregova, None; Š. Forejtová, None; J. Hořínková, None; M. Hušáková, None; M. Tomcik, None; J. Gatterová, None; J. Vencovský, Abbvie, Biogen, Boehringer, Eli Lilly, Gilead, Kezar, Merck, Novartis, Octapharma, Pfizer, Takeda, UCB, Werfen, Argenx; K. Pavelka, MSD, Pfizer, Roche, Eli Lilly, Medac, UCB, SOBI, Biogen, Sandoz, Viatris; L. Šenolt, None; J. Baloun, None.
