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

Joachim Høg Mortensen, Tina Manon-Jensen, Michael Dam Jensen, Per Hägglund, Lone Gabriels Klinge, Jens Kjeldsen, Aleksander Krag, Morten Asser Karsdal, Anne-Christine Bay-Jensen

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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.

Original languageEnglish
Article numbere0185855
JournalPLOS ONE
Volume12
Issue number10
Number of pages16
ISSN1932-6203
DOIs
Publication statusPublished - 2017

Fingerprint

Crohn disease
Irritable Bowel Syndrome
colitis
Ulcerative Colitis
extracellular matrix
Crohn Disease
inflammatory bowel disease
biomarkers
Inflammatory Bowel Diseases
Biomarkers
Complement C5
inflammation
Logistic Models
irritable bowel syndrome
Collagen Type V
Colonic Diseases
immunosuppressive agents
disease surveillance
Immunosuppressive Agents
Nonparametric Statistics

Keywords

  • Adolescent
  • Adult
  • Aged
  • Biomarkers
  • Cohort Studies
  • Colitis, Ulcerative
  • Crohn Disease
  • Diagnosis, Differential
  • Extracellular Matrix
  • Female
  • Humans
  • Irritable Bowel Syndrome
  • Male
  • Middle Aged
  • Young Adult
  • Journal Article

Cite this

Mortensen, Joachim Høg ; Manon-Jensen, Tina ; Jensen, Michael Dam ; Hägglund, Per ; Klinge, Lone Gabriels ; Kjeldsen, Jens ; Krag, Aleksander ; Karsdal, Morten Asser ; Bay-Jensen, Anne-Christine. / 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. In: PLOS ONE. 2017 ; Vol. 12, No. 10.
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title = "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",
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.",
keywords = "Adolescent, Adult, Aged, Biomarkers, Cohort Studies, Colitis, Ulcerative, Crohn Disease, Diagnosis, Differential, Extracellular Matrix, Female, Humans, Irritable Bowel Syndrome, Male, Middle Aged, Young Adult, Journal Article",
author = "Mortensen, {Joachim H{\o}g} and Tina Manon-Jensen and Jensen, {Michael Dam} and Per H{\"a}gglund and Klinge, {Lone Gabriels} and Jens Kjeldsen and Aleksander Krag and Karsdal, {Morten Asser} and Anne-Christine Bay-Jensen",
year = "2017",
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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. / Mortensen, Joachim Høg; Manon-Jensen, Tina; Jensen, Michael Dam; Hägglund, Per; Klinge, Lone Gabriels; Kjeldsen, Jens; Krag, Aleksander; Karsdal, Morten Asser; Bay-Jensen, Anne-Christine.

In: PLOS ONE, Vol. 12, No. 10, e0185855, 2017.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - 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

AU - Mortensen, Joachim Høg

AU - Manon-Jensen, Tina

AU - Jensen, Michael Dam

AU - Hägglund, Per

AU - Klinge, Lone Gabriels

AU - Kjeldsen, Jens

AU - Krag, Aleksander

AU - Karsdal, Morten Asser

AU - Bay-Jensen, Anne-Christine

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - Adolescent

KW - Adult

KW - Aged

KW - Biomarkers

KW - Cohort Studies

KW - Colitis, Ulcerative

KW - Crohn Disease

KW - Diagnosis, Differential

KW - Extracellular Matrix

KW - Female

KW - Humans

KW - Irritable Bowel Syndrome

KW - Male

KW - Middle Aged

KW - Young Adult

KW - Journal Article

U2 - 10.1371/journal.pone.0185855

DO - 10.1371/journal.pone.0185855

M3 - Journal article

VL - 12

JO - P L o S One

JF - P L o S One

SN - 1932-6203

IS - 10

M1 - e0185855

ER -