Whole blood profiling of T-cell derived miRNA allows the development of prognostic models in inflammatory bowel disease

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Whole blood profiling of T-cell derived miRNA allows the development of prognostic models in inflammatory bowel disease

Kalla, R. (författare): MRC Centre for Inflammation Research, Queens Medical Research Institute, University of Edinburgh, United Kingdom,Univ Edinburgh, Scotland

Adams, A. T. (författare): Translational Gastroenterology Unit, Nuffield Department of Medicine, Experimental Medicine Division, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom,Univ Oxford, England

Ventham, N. T. (författare): Institute of Genetics and Molecular Medicine, University of Edinburgh, United Kingdom,Univ Edinburgh, Scotland

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Kennedy, N. A. (författare): Exeter IBD and Pharmacogenetics group, University of Exeter, United Kingdom,Univ Exeter, England

White, R. (författare): Institute of Immunology and Infection Research and Centre for Immunity, Infection & Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom,Univ Edinburgh, Scotland

Clarke, C. (författare): LifeArc, Nine Edinburgh Bioquarter, Edinburgh, United Kingdom,LifeArc, Scotland

Ivens, A. (författare): Institute of Immunology and Infection Research and Centre for Immunity, Infection & Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom,Univ Edinburgh, Scotland

Bergemalm, Daniel, 1977- (författare): Örebro universitet,Institutionen för medicinska vetenskaper,Region Örebro län,Department of Gastroenterology,Orebro Univ, Sweden

Vatn, S. (författare): Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway,Akershus Univ Hosp, Norway

Lopez-Jimena, B. (författare): LifeArc, Nine Edinburgh Bioquarter, Edinburgh, United Kingdom,LifeArc, Scotland

Ricanek, P. (författare): Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway,Akershus Univ Hosp, Norway; Univ Oslo, Norway

Vatn, M. H. (författare): Institute of Clinical Medicine, University of Oslo, Oslo, Norway,Univ Oslo, Norway

Söderholm, Johan D (författare): Linköpings universitet,Avdelningen för kirurgi, ortopedi och onkologi,Medicinska fakulteten,Region Östergötland, Kirurgiska kliniken US

Gomollón, F. (författare): HCU "Lozano Blesa," IIS Aragón, Zaragoza, Spain

Nowak, J. K. (författare): Translational Gastroenterology Unit, Nuffield Department of Medicine, Experimental Medicine Division, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; Department of Paediatric Gastroenterology and Metabolic diseases, Poznan University of Medical Sciences, Poznan, Poland,Univ Oxford, England; Poznan Univ Med Sci, Poland,Akershus Univ Hosp, Norway

Jahnsen, J. (författare): Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway,Orebro Univ, Sweden,Univ Oxford, England; Univ Edinburgh, Scotland

Halfvarson, Jonas, 1970- (författare): Örebro universitet,Institutionen för medicinska vetenskaper,Department of Gastroenterology

McTaggart, S. (författare): LifeArc, Nine Edinburgh Bioquarter, Edinburgh, United Kingdom,LifeArc, Scotland

Ho, G. T. (författare): MRC Centre for Inflammation Research, Queens Medical Research Institute, University of Edinburgh, United Kingdom,Univ Edinburgh, Scotland

Buck, A. (författare): Institute of Immunology and Infection Research and Centre for Immunity, Infection & Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom,Univ Edinburgh, Scotland; Univ Edinburgh, Scotland

Satsangi, J. (författare): Translational Gastroenterology Unit, Nuffield Department of Medicine, Experimental Medicine Division, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; Institute of Genetics and Molecular Medicine, University of Edinburgh, United Kingdom

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2020-06-29
2020
Engelska.
Ingår i: Journal of Crohn's & Colitis. - : Elsevier. - 1873-9946 .- 1876-4479. ; 14:12, s. 1724-1733

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Tidskriftsartikel (refereegranskat)

Abstract Ämnesord

Stäng

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. In our study, we define the cell-specific miRNA profiles and investigate its biomarker potential in IBD.METHODS: In a 2-stage prospective multi-centre case control study, Next Generation sequencing was performed on a discovery cohort of immunomagnetically separated leucocytes from 32 patients (9 CD, 14 UC, 8 healthy controls) and differentially expressed signals were validated in whole blood in 294 patients (97 UC, 98 CD, 98 non-IBD) 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 leucocyte 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 (HR 1.98, 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 2 or more criteria were met and 90% for UC if 3 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Gastroenterologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Gastroenterology and Hepatology (hsv//eng)

Nyckelord

MicroRNA
T-cell
inflammatory bowel disease
crohn's disease
ulcerative colitis
biomarkers
proteins
prognosis
whole blood
mRNA
epigenetics

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Gastroenterologi

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Av lärosätet: Örebro universitet; Linköpings universitet; Karolinska Institutet

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