000106267 001__ 106267
000106267 005__ 20210706112730.0
000106267 0247_ $$2doi$$a10.1093/ecco-jcc/jjaa134
000106267 0248_ $$2sideral$$a122237
000106267 037__ $$aART-2021-122237
000106267 041__ $$aeng
000106267 100__ $$aKalla, R.
000106267 245__ $$aWhole Blood Profiling of T-cell-Derived microRNA Allows the Development of Prognostic models in Inflammatory Bowel Disease
000106267 260__ $$c2021
000106267 5060_ $$aAccess copy available to the general public$$fUnrestricted
000106267 5203_ $$aBackground: 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.
000106267 540__ $$9info:eu-repo/semantics/openAccess$$aAll rights reserved$$uhttp://www.europeana.eu/rights/rr-f/
000106267 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/acceptedVersion
000106267 700__ $$aAdams, A.T.
000106267 700__ $$aVentham, N.T.
000106267 700__ $$aKennedy, N.A.
000106267 700__ $$aWhite, R.
000106267 700__ $$aClarke, C.
000106267 700__ $$aIvens, A.
000106267 700__ $$aBergemalm, D.
000106267 700__ $$aVatn, S.
000106267 700__ $$aLopez-Jimena, B.
000106267 700__ $$aRicanek, P.
000106267 700__ $$aVatn, M.H.
000106267 700__ $$aSöderholm, J.D.
000106267 700__ $$0(orcid)0000-0003-0076-3529$$aGomollón, F.$$uUniversidad de Zaragoza
000106267 700__ $$aNowak, J.K.
000106267 700__ $$aJahnsen, J.
000106267 700__ $$aHalfvarson, J.
000106267 700__ $$aMctaggart, S.
000106267 700__ $$aHo, G.T.
000106267 700__ $$aBuck, A.
000106267 700__ $$aSatsangi, J.
000106267 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina
000106267 773__ $$g14, 12 (2021), 1724-1733$$pJ. Crohns  Colitis$$tJournal of Crohn's & colitis$$x1873-9946
000106267 8564_ $$s868224$$uhttps://zaguan.unizar.es/record/106267/files/texto_completo.pdf$$yPostprint
000106267 8564_ $$s1505907$$uhttps://zaguan.unizar.es/record/106267/files/texto_completo.jpg?subformat=icon$$xicon$$yPostprint
000106267 909CO $$ooai:zaguan.unizar.es:106267$$particulos$$pdriver
000106267 951__ $$a2021-07-06-09:50:16
000106267 980__ $$aARTICLE