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Whole blood profili...
Whole blood profiling of T-cell derived miRNA allows the development of prognostic models in inflammatory bowel disease
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- Kalla, R. (author)
- MRC Centre for Inflammation Research, Queens Medical Research Institute, University of Edinburgh, United Kingdom,Univ Edinburgh, Scotland
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- Adams, A. T. (author)
- Translational Gastroenterology Unit, Nuffield Department of Medicine, Experimental Medicine Division, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom,Univ Oxford, England
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- Ventham, N. T. (author)
- Institute of Genetics and Molecular Medicine, University of Edinburgh, United Kingdom,Univ Edinburgh, Scotland
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- Kennedy, N. A. (author)
- Exeter IBD and Pharmacogenetics group, University of Exeter, United Kingdom,Univ Exeter, England
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- White, R. (author)
- 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
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- Clarke, C. (author)
- LifeArc, Nine Edinburgh Bioquarter, Edinburgh, United Kingdom,LifeArc, Scotland
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- Ivens, A. (author)
- 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
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- Bergemalm, Daniel, 1977- (author)
- Örebro universitet,Institutionen för medicinska vetenskaper,Region Örebro län,Department of Gastroenterology,Orebro Univ, Sweden
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- Vatn, S. (author)
- Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway,Akershus Univ Hosp, Norway
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- Lopez-Jimena, B. (author)
- LifeArc, Nine Edinburgh Bioquarter, Edinburgh, United Kingdom,LifeArc, Scotland
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- Ricanek, P. (author)
- Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway,Akershus Univ Hosp, Norway; Univ Oslo, Norway
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- Vatn, M. H. (author)
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway,Univ Oslo, Norway
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- Söderholm, Johan D (author)
- Linköpings universitet,Avdelningen för kirurgi, ortopedi och onkologi,Medicinska fakulteten,Region Östergötland, Kirurgiska kliniken US
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- Gomollón, F. (author)
- HCU "Lozano Blesa," IIS Aragón, Zaragoza, Spain
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- Nowak, J. K. (author)
- 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
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- Jahnsen, J. (author)
- Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway,Orebro Univ, Sweden,Univ Oxford, England; Univ Edinburgh, Scotland
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- Halfvarson, Jonas, 1970- (author)
- Örebro universitet,Institutionen för medicinska vetenskaper,Department of Gastroenterology
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- McTaggart, S. (author)
- LifeArc, Nine Edinburgh Bioquarter, Edinburgh, United Kingdom,LifeArc, Scotland
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- Ho, G. T. (author)
- MRC Centre for Inflammation Research, Queens Medical Research Institute, University of Edinburgh, United Kingdom,Univ Edinburgh, Scotland
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- Buck, A. (author)
- 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
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- Satsangi, J. (author)
- 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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(creator_code:org_t)
- 2020-06-29
- 2020
- English.
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In: Journal of Crohn's & Colitis. - : Elsevier. - 1873-9946 .- 1876-4479. ; 14:12, s. 1724-1733
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Gastroenterologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Gastroenterology and Hepatology (hsv//eng)
Keyword
- MicroRNA
- T-cell
- inflammatory bowel disease
- crohn's disease
- ulcerative colitis
- biomarkers
- proteins
- prognosis
- whole blood
- mRNA
- epigenetics
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Kalla, R.
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Adams, A. T.
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Ventham, N. T.
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Kennedy, N. A.
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White, R.
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Clarke, C.
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show more...
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Ivens, A.
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Bergemalm, Danie ...
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Vatn, S.
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Lopez-Jimena, B.
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Ricanek, P.
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Vatn, M. H.
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Söderholm, Johan ...
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Gomollón, F.
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Nowak, J. K.
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Jahnsen, J.
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Halfvarson, Jona ...
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McTaggart, S.
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Ho, G. T.
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Buck, A.
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Satsangi, J.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Gastroenterology ...
- Articles in the publication
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Journal of Crohn ...
- By the university
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Örebro University
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Linköping University
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Karolinska Institutet