BackgroundmicroRNAs (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].ObjectivesThe 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.MethodsMassive 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 SpondylitisSpineScore (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.ResultsMPS 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.ConclusionThis 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.AcknowledgementsSupported by MHCR No. 023728, BBMRI-CZ LM2018125 and SVV 260 523.Disclosure of InterestsNone Declared.
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
BackgroundBiologic (b-) and targeted synthetic (ts-) disease-modifying antirheumatic drugs (DMARDs) have brought significant progress in the treatment of rheumatoid arthritis (RA), but a significant proportion of RA patients still remain symptomatic despite treatment according to current recommendations. These patients have recently been defined as “difficult-to-treat (D2T)” RA (1). There is evidence that miRNA expression may play a role in the diagnosis and therapy of RA (2).ObjectivesIn a retrospective study, we analyzed patients’ blood samples prior to b-/ts-DMARD treatment and profiled circulating miRNAs to predict the development of D2T-RA.MethodsA total of 36 patients fulfilling the EULAR definition of D2T-RA (1) (mean age 59.1±10.7 yrs, 78% females), 36 patients with RA in sustained clinical remission on b-/ts-DMARDs at two consecutive examinations 12 wks apart (mean age 66.3±9.6 yrs, 78% females), and 36 healthy controls (mean age 61.1±7.7 yrs, 68% females) were included in the study. Blood samples were collected before initiation of b-/ts-DMARD. We profiled circulating miRNAs using the sequencing approach and differential expression analysis was performed using DESeq2 algorithm.ResultsThe massive parallel sequencing of circulating miRNAs detected 814 quantifiable miRNAs and DESeq2 algorithm revealed 35 miRNAs with different concentrations in patients who developed D2T-RA compared to patients with RA who achieved sustained remission or healthy controls. Out of these miRNAs, miR-16-5p (1.5x) and miR-451a (2.1x) were downregulated and miR-126-3p (1.4x) was upregulated in D2T RA patients compared to controls. In addition, miR-101-3p (1.5x) was downregulated in D2T RA compared to RA patients. Except for miR-101-3p, these miRNAS have been previously associated with RA and might predict development of D2T disease prior to initiation of b-/ts-DMARD therapy.ConclusionWe found four miRNAs as potential biomarkers differentiating patients who are at risk to develop difficult-to-treat disease compared to patients who have a chance of sustained remission even before initiation of biological or targeted synthetic DMARDs. Further studies with larger sample size are needed to validated these data.References[1]Nagy G, Roodenrijs NMT, Welsing PM, et al. EULAR definition of difficult-to-treat rheumatoid arthritis. Ann Rheum Dis. 2021 Jan;80(1):31-35.[2]Filková M, Jüngel A, Gay RE, Gay S. MicroRNAs in rheumatoid arthritis: potential role in diagnosis and therapy. BioDrugs. 2012 Jun 1;26(3):131-41.AcknowledgementsThis work was supported by the project SVV 260 523, BBMRI-CZ LM2018125, and a project of the MHCR for conceptual research development No. 023728.Disclosure of InterestsNone declared.
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