To Örebro University

oru.seÖrebro University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Preclinical protein signatures in blood predict Crohn's disease and Ulcerative colitis several years before the diagnosis
Örebro University, Faculty of Medicine and Health-Department of Laboratory Medicine-Clinical Microbiology, Örebro, Sweden.
Örebro University, School of Medical Sciences.
Örebro University, Faculty of Medicine and Health, School of Medical Sciences, Örebro, Sweden.
Karolinska Institutet, Department of Medicine Solna, Stockholm, Sweden.
Show others and affiliations
2024 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 18, no Suppl. 1, p. I660-I661, article id P296Article in journal, Meeting abstract (Other academic) Published
Abstract [en]

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).

Place, publisher, year, edition, pages
Oxford University Press, 2024. Vol. 18, no Suppl. 1, p. I660-I661, article id P296
National Category
Gastroenterology and Hepatology
Identifiers
URN: urn:nbn:se:oru:diva-112974DOI: 10.1093/ecco-jcc/jjad212.0426ISI: 001189928900420OAI: oai:DiVA.org:oru-112974DiVA, id: diva2:1849942
Conference
9th Congress of ECCO, Stockholm, Sweden, February 21-24, 2024
Available from: 2024-04-09 Created: 2024-04-09 Last updated: 2025-02-11Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full text

Authority records

Salomon, BenitaDannenberg, KatharinaAndersson, ErikEriksson, CarlKruse, RobertCao, YangRepsilber, DirkBergemalm, DanielHalfvarson, Jonas

Search in DiVA

By author/editor
Salomon, BenitaDannenberg, KatharinaAndersson, ErikEriksson, CarlKruse, RobertCao, YangRepsilber, DirkBergemalm, DanielHalfvarson, Jonas
By organisation
School of Medical SciencesÖrebro University Hospital
In the same journal
Journal of Crohn's & Colitis
Gastroenterology and Hepatology

Search outside of DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 96 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf