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Whole Blood Profiling of T-cell-Derived microRNA Allows the Development of Prognostic models in Inflammatory Bowel Disease.
Kalla, 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, Johan D; Gomollón, F; Nowak, J K; Jahnsen, J; Halfvarson, J; McTaggart, S; Ho, G T; Buck, A; Satsangi, J.
Afiliación
  • Kalla R; MRC Centre for Inflammation Research, Queens Medical Research Institute, University of Edinburgh, Edinburgh, UK.
  • Adams AT; Translational Gastroenterology Unit, Nuffield Department of Medicine, Experimental Medicine Division, University of Oxford, John Radcliffe Hospital, Oxford, UK.
  • Ventham NT; Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
  • Kennedy NA; Exeter IBD and Pharmacogenetics group, University of Exeter, Exeter, UK.
  • White R; Institute of Immunology and Infection Research and Centre for Immunity, Infection & Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh, UK.
  • Clarke C; LifeArc, Nine Edinburgh Bioquarter, Edinburgh, UK.
  • Ivens A; Institute of Immunology and Infection Research and Centre for Immunity, Infection & Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh, UK.
  • Bergemalm D; Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
  • Vatn S; Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway.
  • Lopez-Jimena B; LifeArc, Nine Edinburgh Bioquarter, Edinburgh, UK.
  • Ricanek P; Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway.
  • Vatn MH; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
  • Söderholm JD; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
  • Gomollón F; Department of Surgery and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
  • Nowak JK; HCU 'Lozano Blesa', IIS Aragón, Zaragoza, Spain.
  • Jahnsen J; Translational Gastroenterology Unit, Nuffield Department of Medicine, Experimental Medicine Division, University of Oxford, John Radcliffe Hospital, Oxford, UK.
  • Halfvarson J; Department of Paediatric Gastroenterology and Metabolic diseases, Poznan University of Medical Sciences, Poznan, Poland.
  • McTaggart S; Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway.
  • Ho GT; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
  • Buck A; Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
  • Satsangi J; LifeArc, Nine Edinburgh Bioquarter, Edinburgh, UK.
J Crohns Colitis ; 14(12): 1724-1733, 2020 Dec 02.
Article en En | MEDLINE | ID: mdl-32598439
BACKGROUND: 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T / Enfermedades Inflamatorias del Intestino / MicroARNs / Imagen de Cuerpo Entero Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: J Crohns Colitis Asunto de la revista: GASTROENTEROLOGIA Año: 2020 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T / Enfermedades Inflamatorias del Intestino / MicroARNs / Imagen de Cuerpo Entero Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: J Crohns Colitis Asunto de la revista: GASTROENTEROLOGIA Año: 2020 Tipo del documento: Article Pais de publicación: Reino Unido