Ulcerative colitis, Crohn's disease, and irritable bowel syndrome have different profiles of extracellular matrix turnover, which also reflects disease activity in Crohn's disease

PLoS One. 2017 Oct 13;12(10):e0185855. doi: 10.1371/journal.pone.0185855. eCollection 2017.

Abstract

Background: Increased protease activity is a key pathological feature of inflammatory bowel disease (IBD). However, the differences in extracellular matrix remodelling (ECM) in Crohn's disease (CD) and ulcerative colitis (UC) are not well described. An increased understanding of the inflammatory processes may provide optimized disease monitoring and diagnostics. We investigated the tissue remodelling in IBD and IBS patients by using novel blood-based biomarkers reflecting ECM remodelling.

Methods: Five ECM biomarkers (VICM, BGM, EL-NE, C5M, Pro-C5) were measured by competitive ELISAs in serum from 72 CD patients, 60 UC patients, 22 patients with irritable bowel syndrome (IBS), and 24 healthy donors. One-way analysis of variance, Mann-Whitney U-test, logistic regression models, and receiver operator characteristics (ROC) curve analysis was carried out to evaluate the diagnostic accuracy of the biomarkers.

Results: The ECM remodelling was significantly different in UC compared to CD. The best biomarker combination to differentiate UC from CD and colonic CD was BGM and VICM (AUC = 0.98, P<0.001; AUC = 0.97, P<0.001), and the best biomarker combination to differentiate IBD from IBS patients were BGM, EL-NE, and Pro-C5 (AUC = 0.8, P<0.001). When correcting for the use of immunosuppressant and elevated CRP levels (CRP>5mg/mL), correlation of Pro-C5 (r = 0.36) with CDAI was slightly improved compared to CRP (r = 0.27) corrected for the use of immunosuppressant. Furthermore, BGM and EL-NE biomarkers were highly associated with colon inflammation in CD patients.

Conclusion: ECM fragments of tissue remodelling in IBD affect UC and CD differently, and may aid in differentiating IBD from IBS (EL-NE, BGM, Pro-C5), and UC from CD patients (BGM, VICM). Formation of type V collagen is related to the level of inflammation in CD and may reflect disease activity in CD.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers / blood
  • Cohort Studies
  • Colitis, Ulcerative / blood
  • Colitis, Ulcerative / diagnosis
  • Colitis, Ulcerative / pathology*
  • Crohn Disease / blood
  • Crohn Disease / diagnosis
  • Crohn Disease / pathology*
  • Diagnosis, Differential
  • Extracellular Matrix / pathology*
  • Female
  • Humans
  • Irritable Bowel Syndrome / blood
  • Irritable Bowel Syndrome / diagnosis
  • Irritable Bowel Syndrome / pathology*
  • Male
  • Middle Aged
  • Young Adult

Substances

  • Biomarkers

Grants and funding

This work was funded by the Danish Research Foundation. The funder provided support to the research in the form of research materials, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. Joachim H. Mortensen, Tina Manon-Jensen, Morten A. Karsdal and Anne C. Bay-Jensen commercial affiliation with Nordic Bioscience did not play a role in conducting the study, as this study was purely scientific driven and study protocols and design of the study was approved by all authors, including authors not affiliated with Nordic Bioscience. Nordic Bioscience or the Danish Research Foundation did not in any way fund the following authors Michael D. Jensen, Per Hägglund, Lone G. Klinge, Jens Kjeldsen, and Aleksander Krag.with Nordic Bioscience did not play a role in conducting the study, as this study was purely scientific driven and study protocols and design of the study was approved by all authors, including authors not affiliated with Nordic Bioscience. Nordic Bioscience or the Danish Research Foundation did not in any way fund the following authors Michael D. Jensen, Per Hägglund, Lone G. Klinge, Jens Kjeldsen, and Aleksander Krag.