FRI0165 Micrornas dysregulation in monocytes and t cd4 lymphocytes from patients with axial spondyloarthritis
Authors: O. Fogel, A. Bugge Tingaard, M. Fagny, N. Sigrist, E. Roché, L. Leclère, J.-F. Deleuze, M. Dougados, C. Miceli-Richard, J. Tost
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> MicroRNAs have been shown to play a crucial role during innate or adaptive immune response. Dysregulation of miRNAs has been described in several autoimmune or rheumatic diseases including rheumatoid arthritis, inflammatory bowel disease or psoriasis. In spondyloarthritis (SpA), only few studies on miR expression have been reported with highly diverse methodologies and involving small samples of patients. <h3>Objectives</h3> Because T CD4 lymphocytes and monocytes are important cells in SpA pathophysiology, we wanted to assess the miR expression profile in these two cell types sorted from axial SpA (AxSpA) patients. <h3>Methods</h3> Eighty one AxSpA patients were included in this study. Among these patients, 74 fulfilled the ASAS classification criteria (imaging arm) with sacro-iliitis on X-rays (n=56) or objective signs of inflammation on MRI (n=18). Two independent cohorts of 22 and 59 SpA patients were compared to 17 and 38 age and sex-matched controls. Both SpA patients and controls were recruited from October 2014 to July 2017 in the department of rheumatology at Cochin Hospital in Paris, France. All SpA patients had an active disease despite NSAIDs intake (mean BASDAI score of 49±19 and mean ASDAS score of 3±0.9), were free of any biologic treatment and were eligible for a TNF-blocker treatment. Seventy-seven percent were HLA-B27 positive. T lymphocytes and monocytes were isolated from PBMC by direct isolation with magnetic microbeads (CD4 +and CD14+). Three-hundred seventy two miRs were screened by q-RT-PCR on the exploratory cohort and only MiRs showing a significant differential expression in the first cohort were analysed in the validation cohort. An unpaired T-test was used for comparison of miR expression level. <h3>Results</h3> In the exploratory cohort, 51 (CD14+) and 70 miRs (CD4+) were found to be differentially expressed between patients and controls. Among these, 15 miRs (in CD14+), and 12 miRs (in CD4+) were also found dysregulated in the validation cohort. These validated miRNAs were found to play a key role in physiological pathways such as NFkB or TGFb, Wnt signalling and monocyte differentiation that have been involved in the pathophysiology of the disease. Neither clinical subphenotypes nor biological parameters were associated with different profiles of miR expression after adjusting for multiple tests. We found a negative correlation between miR-146a-5p level and BASDAI (r=-0.28, p=0.011) and ASDAS (r=-0.38, p=5.9 10–4) in monocytes. <h3>Conclusions</h3> We found a dysregulation of miR expression in monocytes and T CD4 lymphocytes from patients with axial spondyloarthritis, whose consequences could contribute to the pathophysiology of the disease and be of interest for therapeutic perspective. Moreover, identifying biomarkers with the potential of diagnostic signature should help the clinician in daily practice. <h3>Disclosure of Interest</h3> None declared