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  • Grännö, O.Örebro University, Faculty of Medicine and Health-Department of Laboratory Medicine-Clinical Microbiology, Örebro, Sweden (författare)

Preclinical protein signatures in blood predict Crohn's disease and Ulcerative colitis several years before the diagnosis

  • Artikel/kapitelEngelska2024

Förlag, utgivningsår, omfång ...

  • Oxford University Press,2024
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:oru-112974
  • https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-112974URI
  • https://doi.org/10.1093/ecco-jcc/jjad212.0426DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

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

Anmärkningar

  • Background: We aimed to identify protein signatures predictive of a future diagnosis of inflammatory bowel disease (IBD).Methods: We conducted a case-control study, nested within large population-based cohorts with biorepositories. Samples were obtained from individuals who later in life were diagnosed with IBD (preclinical cases) and compared with age and sex-matched individuals who remained free from IBD during follow-up (controls). Using proximity extension assays (Olink, Uppsala), we measured 176 proteins. We applied regularized logistic regression to identify protein signatures of preclinical disease in serum from the discovery cohort (n=312). Their performance was validated in an external preclinical cohort (n=222). The biological relevance of identified proteins was further assessed in an inception cohort (n=144). Finally, we used an IBD twin cohort (n=327) to examine the impact of genetic and shared environmental factors on identified proteins.Results: We identified 34 proteins associated with preclinical Crohn’s disease (CD) in the discovery cohort (Pfalse discovery rate <0.10), with 9 confirmed in the validation cohort (Pfalse discovery rate <0.05). For preclinical ulcerative colitis (UC), 45 proteins were identified and 12 validated (Fig. 1A-B). In the discovery cohort, a signature of 29 proteins differentiated preclinical CD cases from controls with an AUC of 0.85 (Fig. 1G). Its performance was confirmed when applied to the preclinical validation cohort (AUC=0.84, Fig. 1H). Moreover, the signature had excellent capacity to differentiate newly diagnosed CD from healthy controls in the inception cohort (AUC = 0.99, Fig. 1I). The preclinical UC signature had a significant, but albeit lower, predictive capacity in the discovery (AUC=0.77), validation (AUC=0.67) and inception cohort (AUC=0.90, Fig. 1G-I).15 of 17 proteins associated with preclinical IBD demonstrated significantly higher intra-pair correlation coefficients in healthy monozygotic- compared to dizygotic twin pairs, indicating an influence from genetic factors on the regulation of these protein markers. The preclinical signature for CD demonstrated an AUC of 0.87 when comparing twins with preclinical CD (n=10) to matched external healthy twins. However, its predictive capacity was lower when comparing preclinical CD twins with their healthy twin siblings (AUC=0.58), i.e., when accounting for genetic and shared environmental factors. The difference in AUC estimates in the twin cohort was not significant (P=0.07).

Ämnesord och genrebeteckningar

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

  • Salomon, Benita,1993-Örebro universitet,Institutionen för medicinska vetenskaper(Swepub:oru)basn (författare)
  • Lindqvist, C. M.Örebro University, Faculty of Medicine and Health, School of Medical Sciences, Örebro, Sweden (författare)
  • Hedin, C. R. H.Karolinska Institutet, Department of Medicine Solna, Stockholm, Sweden (författare)
  • Carlson, M.Uppsala University, Department of Medical Sciences, Gastroenterology Research Group, Uppsala, Sweden (författare)
  • Dannenberg, Katharina,1991-Örebro universitet,Institutionen för medicinska vetenskaper(Swepub:oru)kadg (författare)
  • Andersson, Erik,1988-Örebro universitet,Institutionen för medicinska vetenskaper,Department of Gastroenterology(Swepub:oru)edan (författare)
  • Söderholm, J. D.Linköping University, Department of Surgery, Linköping, Sweden (författare)
  • Keita, Å. V.Linköping University, Department of Biomedical and Clinical Sciences, Linköping, Sweden (författare)
  • Öhman, L.Sahlgrenska Academy, University of Gothenburg, Department of Microbiology and Immunology, Institute of Biomedicine, Göteborg, Sweden (författare)
  • Magnusson, M. K.Sahlgrenska Academy, University of Gothenburg, Department of Microbiology and Immunology, Institute of Biomedicine, Göteborg, Sweden (författare)
  • D'Amato, M.CIC BioGUNE–BRTA, Gastrointestinal Genetics Lab, Derio, Spain (författare)
  • Eriksson, Carl,1981-Örebro universitet,Institutionen för medicinska vetenskaper,Region Örebro län,Department of Gastroenterology(Swepub:oru)clen (författare)
  • Hultdin, J.Umeå University, Department of Medical Biosciences, Clinical Chemistry, Umeå, Sweden (författare)
  • Kruse, Robert,1972-Örebro universitet,Institutionen för medicinska vetenskaper(Swepub:oru)rke (författare)
  • Cao, Yang,Associate Professor,1972-Örebro universitet,Institutionen för medicinska vetenskaper,Region Örebro län,Clinical Epidemiology and Biostatistics(Swepub:oru)yco (författare)
  • Repsilber, Dirk,1971-Örebro universitet,Institutionen för medicinska vetenskaper(Swepub:oru)drr (författare)
  • Bergemalm, Daniel,1977-Örebro universitet,Institutionen för medicinska vetenskaper,Region Örebro län,Department of Gastroenterology(Swepub:oru)dbm (författare)
  • Grip, O.Skåne University Hospital, Department of Gastroenterology, Malmö, Sweden (författare)
  • Karling, P.Umeå University, Department of Public Health and Clinical Medicine, Umeå, Sweden (författare)
  • Halfvarson, Jonas,1970-Örebro universitet,Institutionen för medicinska vetenskaper,Department of Gastroenterology(Swepub:oru)jshn (författare)
  • Örebro University, Faculty of Medicine and Health-Department of Laboratory Medicine-Clinical Microbiology, Örebro, SwedenInstitutionen för medicinska vetenskaper (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Journal of Crohn's & Colitis: Oxford University Press18:Suppl. 1, s. I660-I6611873-99461876-4479

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