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Serum proteomic profiling at diagnosis predicts clinical course, and need for intensification of treatment in inflammatory bowel disease

Kalla, R. (författare)
Institute of Genetics and Molecular Medicine, University of Edinburgh, United Kingdom; MRC Centre for Inflammation Research, Queens Medical Research Institute, University of Edinburgh, United Kingdom,Univ Edinburgh, Scotland; Univ Edinburgh, Scotland
Adams, A. T. (författare)
Institute of Genetics and Molecular Medicine, University of Edinburgh, United Kingdom; Translational Gastroenterology Unit, Nuffield Department of Medicine, Experimental Medicine Division, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom,Univ Edinburgh, Scotland; Univ Oxford, England
Bergemalm, Daniel, 1977- (författare)
Örebro universitet,Institutionen för medicinska vetenskaper,Region Örebro län,Department of Gastroenterology,Orebro Univ, Sweden
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Vatn, S. (författare)
Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway,Akershus Univ Hosp, Norway
Kennedy, N. A. (författare)
Institute of Genetics and Molecular Medicine, University of Edinburgh, United Kingdom; Exeter IBD and Pharmacogenetics group, University of Exeter, United Kingdom,Univ Edinburgh, Scotland; Univ Exeter, England
Ricanek, P. (författare)
Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway; Institute of Clinical Medicine, Campus Ahus, University of Oslo, Oslo, Norway,Univ Edinburgh, Scotland; Univ Oslo, Norway
Lindstrom, J. (författare)
Health Services Research Unit, Akershus University Hospital, Lørenskog, Norway; Institute of Clinical Medicine, Campus Ahus, University of Oslo, Oslo, Norway,Akershus Univ Hosp, Norway; Univ Oslo, Norway
Ocklind, A. (författare)
Olink Proteomics, Uppsala, Sweden,Olink Prote, Sweden
Hjelm, F. (författare)
Olink Proteomics, Uppsala, Sweden,Olink Prote, Sweden
Ventham, N. T. (författare)
Institute of Genetics and Molecular Medicine, University of Edinburgh, United Kingdom,Univ Edinburgh, Scotland
Ho, G. T. (författare)
MRC Centre for Inflammation Research, Queens Medical Research Institute, University of Edinburgh, United Kingdom,Univ Edinburgh, Scotland
Petren, C. (författare)
Olink Proteomics, Uppsala, Sweden,Olink Prote, Sweden
Repsilber, Dirk, 1971- (författare)
Örebro universitet,Institutionen för medicinska vetenskaper,Orebro Univ, Sweden
Söderholm, Johan D (författare)
Linköpings universitet,Avdelningen för kirurgi, ortopedi och onkologi,Medicinska fakulteten,Region Östergötland, Kirurgiska kliniken US
Pierik, M. (författare)
Maastricht University Medical Centre (MUMC), Department of Gastroenterology and Hepatology, Maastricht, Netherlands,Maastricht Univ Med Ctr MUMC, Netherlands
D'Amato, M. (författare)
Biocruces Health Research Institute, Molecular Genetics of Digestive Diseases, Cruces, Bilbao, Spain; School of Biological Sciences, Monash University, Victoria, Australia,Basque Fdn Sci, Spain; Basque Fdn Sci, Spain; Monash Univ, Australia
Gomollón, F. (författare)
HCU "Lozano Blesa," IIS Aragón, Zaragoza, Spain
Olbjorn, C. (författare)
Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway; Institute of Clinical Medicine, Campus Ahus, University of Oslo, Oslo, Norway,Akershus Univ Hosp, Norway; Univ Oslo, Norway
Jahnsen, J. (författare)
Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway; Institute of Clinical Medicine, Campus Ahus, University of Oslo, Oslo, Norway,Akershus Univ Hosp, Norway; Univ Oslo, Norway,Orebro Univ, Sweden,Univ Edinburgh, Scotland; Univ Oxford, England
Vatn, M. H. (författare)
Department of Gastroenterology, Akershus UnInstitute of Clinical Medicine, Campus Ahus, University of Oslo, Oslo, Norway,Univ Oslo, Norway
Halfvarson, Jonas, 1970- (författare)
Örebro universitet,Institutionen för medicinska vetenskaper,Department of Gastroenterology
Satsangi, J. (författare)
Institute of Genetics and Molecular Medicine, University of Edinburgh, United Kingdom; Translational Gastroenterology Unit, Nuffield Department of Medicine, Experimental Medicine Division, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom
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 (creator_code:org_t)
2020-11-17
2021
Engelska.
Ingår i: Journal of Crohn's & Colitis. - : Elsevier. - 1873-9946 .- 1876-4479. ; 15:5, s. 699-708
Relaterad länk:
https://www.ncbi.nlm...
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https://urn.kb.se/re...
https://doi.org/10.1...
https://urn.kb.se/re...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • BACKGROUND: Success in personalised medicine in complex disease is critically dependent on biomarker discovery. We profiled serum proteins using a novel proximity extension assay (PEA) to identify diagnostic and prognostic biomarkers in inflammatory bowel disease (IBD).METHODS: We conducted a prospective case-control study in an inception cohort of 552 patients (328 IBD, 224 non-IBD), profiling proteins recruited across 6 centres. Treatment escalation was characterised by the need for biological agents or surgery after initial disease remission. Nested leave-one-out cross validation was used to examine the performance of diagnostic and prognostic proteins.RESULTS: A total of 66 serum proteins differentiated IBD from symptomatic non-IBD controls including MMP-12 (Holm adjusted p=4.1×10 -23 ) and OSM (p=3.7×10 -16). Nine of these proteins associate with cis- germline variation (59 independent SNPs). Fifteen proteins, all members of TNF independent pathways including IL-1 and OSM predicted escalation, over a median follow-up of 518 (IQR 224-756) days. Nested cross-validation of the entire data set allows characterisation of 5-protein-models (96% comprising five core proteins ITGAV, EpCAM, IL18, SLAMF7, and IL8) which define a high-risk subgroup in IBD (HR 3.90, CI: 2.43-6.26), or allows distinct 2, and 3 protein models for UC and CD respectively.CONCLUSION: We have characterised a simple oligo-protein panel that has the potential to identify IBD from symptomatic controls and to predict future disease course. Further prospective work is required to validate our findings.

Ämnesord

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

Nyckelord

Crohn's disease
OSM
genetics
inflammatory bowel diseases (IBD)
outcomes
prognosis
protein quantitative trait loci
proteins
proximity extension assay
ulcerative colitis

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