OP0105 miRNOME PROFILE IN PATIENTS WITH AXIAL SPONDYLOARTHRITIS

Autor: A. Pekacova, J. Baloun, K. Bubova, M. Gregová, S. Forejtova, J. Horinkova, M. Husakova, M. Tomčík, J. Gatterova, J. Vencovský, K. Pavelka, L. Šenolt
Rok vydání: 2022
Předmět:
Zdroj: Annals of the Rheumatic Diseases. 81:69-69
ISSN: 1468-2060
0003-4967
DOI: 10.1136/annrheumdis-2022-eular.5213
Popis: BackgroundmicroRNAs (miRNAs) are small non-coding RNAs regulating up to 60 % of human mRNAs, including genes related to axial spondyloarthritis (axSpA) (1).ObjectivesThis study aims to profile miRNome and to identify candidate miRNAs determining disease severity in patietns with non-radiographic (nr) and radiographic (r) axSpA.MethodsThe miRNome profiling experiment included peripheral blood mononuclear cells (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 141 subjects (47 patients with nr-axSpA, 44 patients with r-axSpA and 50 healthy controls). We employed the DESeq2 algorithm and generalized linear modelling with a negative binomial assumption (GLM-NB) to evaluate the association of candidate miRNAs to axSpA subtype and clinical disease activity (ASDAS and CRP).ResultsMPS revealed 432 unique miRNAs in all samples. We identified 13 differently expressed miRNAs in axSpA patients compared to healthy controls, and 14 differently expressed miRNAs in axSpA patients with high to very high ASDAS compared to patients with inactive disease. Data from validation cohort revealed that the expression level of miR-4286 was higher in patients with very high disease activity compared to patients with inactive disease. Simultaneously, miR-4286 positively correlated with ASDAS. miR-4286 has been recently associated with osteogenesis and angiogenesis (2). None of the validated miRNAs was associated with the levels of CRP.ConclusionIn this study, we identified that miR-4286 is related to disease activity and could play a role in the pathogenesis of axSpA.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.[2]Yu H, Wang K, Liu P, et al. miR-4286 functions in osteogenesis and angiogenesis via targeting histone deacetylase 3 and alleviates alcohol-induced bone loss in mice. Cell Prolif. 2021 Jun;54(6):e13054.AcknowledgementsSupported by MHCR No. 023728, BBMRI-CZ LM2018125 and SVV 260 523.Disclosure of InterestsNone declared
Databáze: OpenAIRE