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  • Kalla, R.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 (författare)

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

  • Artikel/kapitelEngelska2021

Förlag, utgivningsår, omfång ...

  • 2020-11-17
  • Elsevier,2021
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:oru-87457
  • https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-87457URI
  • https://doi.org/10.1093/ecco-jcc/jjaa230DOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-176483URI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • Funding Agencies|EU FP7 grant: IBD-CHARACTER [2858546]; Wellcome TrustWellcome TrustEuropean Commission
  • 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 och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Adams, A. T.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 (författare)
  • Bergemalm, Daniel,1977-Örebro universitet,Institutionen för medicinska vetenskaper,Region Örebro län,Department of Gastroenterology,Orebro Univ, Sweden(Swepub:oru)dbm (författare)
  • Vatn, S.Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway,Akershus Univ Hosp, Norway (författare)
  • Kennedy, N. A.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 (författare)
  • Ricanek, P.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 (författare)
  • Lindstrom, J.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 (författare)
  • Ocklind, A.Olink Proteomics, Uppsala, Sweden,Olink Prote, Sweden (författare)
  • Hjelm, F.Olink Proteomics, Uppsala, Sweden,Olink Prote, Sweden (författare)
  • Ventham, N. T.Institute of Genetics and Molecular Medicine, University of Edinburgh, United Kingdom,Univ Edinburgh, Scotland (författare)
  • Ho, G. T.MRC Centre for Inflammation Research, Queens Medical Research Institute, University of Edinburgh, United Kingdom,Univ Edinburgh, Scotland (författare)
  • Petren, C.Olink Proteomics, Uppsala, Sweden,Olink Prote, Sweden (författare)
  • Repsilber, Dirk,1971-Örebro universitet,Institutionen för medicinska vetenskaper,Orebro Univ, Sweden(Swepub:oru)drr (författare)
  • Söderholm, Johan DLinköpings universitet,Avdelningen för kirurgi, ortopedi och onkologi,Medicinska fakulteten,Region Östergötland, Kirurgiska kliniken US(Swepub:liu)sodda63 (författare)
  • Pierik, M.Maastricht University Medical Centre (MUMC), Department of Gastroenterology and Hepatology, Maastricht, Netherlands,Maastricht Univ Med Ctr MUMC, Netherlands (författare)
  • D'Amato, M.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 (författare)
  • Gomollón, F.HCU "Lozano Blesa," IIS Aragón, Zaragoza, Spain (författare)
  • Olbjorn, C.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 (författare)
  • Jahnsen, J.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 (författare)
  • Vatn, M. H.Department of Gastroenterology, Akershus UnInstitute of Clinical Medicine, Campus Ahus, University of Oslo, Oslo, Norway,Univ Oslo, Norway (författare)
  • Halfvarson, Jonas,1970-Örebro universitet,Institutionen för medicinska vetenskaper,Department of Gastroenterology(Swepub:oru)jshn (författare)
  • Satsangi, J.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 (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 KingdomUniv Edinburgh, Scotland; Univ Edinburgh, Scotland (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Journal of Crohn's & Colitis: Elsevier15:5, s. 699-7081873-99461876-4479

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