doi:10.1093/ecco-jcc/jjaa134engKalla, R.Adams, A.T.Ventham, N.T.Kennedy, N.A.White, R.Clarke, C.Ivens, A.Bergemalm, D.Vatn, S.Lopez-Jimena, B.Ricanek, P.Vatn, M.H.Söderholm, J.D.Gomollón, F.Nowak, J.K.Jahnsen, J.Halfvarson, J.Mctaggart, S.Ho, G.T.Buck, A.Satsangi, J.Whole Blood Profiling of T-cell-Derived microRNA Allows the Development of Prognostic models in Inflammatory Bowel DiseaseART-2021-122237Background: MicroRNAs [miRNAs] are cell-specific small non-coding RNAs that can regulate gene expression and have been implicated in inflammatory bowel disease [IBD] pathogenesis. Here we define the cell-specific miRNA profiles and investigate its biomarker potential in IBD. Methods: In a two-stage prospective multi-centre case control study, next generation sequencing was performed on a discovery cohort of immunomagnetically separated leukocytes from 32 patients (nine Crohn''s disease [CD], 14 ulcerative colitis [UC], eight healthy controls) and differentially expressed signals were validated in whole blood in 294 patients [97 UC, 98 CD, 98 non-IBD, 1 IBDU] using quantitative PCR. Correlations were analysed with phenotype, including need for early treatment escalation as a marker of progressive disease using Cox proportional hazards. Results: In stage 1, each leukocyte subset [CD4+ and CD8+ T-cells and CD14+ monocytes] was analysed in IBD and controls. Three specific miRNAs differentiated IBD from controls in CD4+ T-cells, including miR-1307-3p [p = 0.01], miR-3615 [p = 0.02] and miR-4792 [p = 0.01]. In the extension cohort, in stage 2, miR-1307-3p was able to predict disease progression in IBD (hazard ratio [HR] 1.98, interquartile range [IQR]: 1.20-3.27; logrank p = 1.80 × 10-3), in particular CD [HR 2.81; IQR: 1.11-3.53, p = 6.50 × 10-4]. Using blood-based multimarker miRNA models, the estimated chance of escalation in CD was 83% if two or more criteria were met and 90% for UC if three or more criteria are met. Interpretation: We have identified and validated unique CD4+ T-cell miRNAs that are differentially regulated in IBD. These miRNAs may be able to predict treatment escalation and have the potential for clinical translation; further prospective evaluation is now indicated.2021http://zaguan.unizar.es/record/10626710.1093/ecco-jcc/jjaa134http://zaguan.unizar.es/record/106267oai:zaguan.unizar.es:106267Journal of Crohn's & colitis 14, 12 (2021), 1724-1733All rights reservedhttp://www.europeana.eu/rights/rr-f/info:eu-repo/semantics/openAccess