Fragments of Citrullinated and MMP-degraded Vimentin and MMP-degraded Type III Collagen Are Novel Serological Biomarkers to Differentiate Crohn's Disease from Ulcerative Colitis

Joachim Høg Mortensen, Line Elbjerg Godskesen, Michael Dam Jensen, Wouter Tobias Van Haaften, Lone Gabriels Klinge, Peter Olinga, Gerard Dijkstra, Jens Kjeldsen, Morten Asser Karsdal, Anne-Christine Bay-Jensen, Aleksander Krag

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

BACKGROUND AND AIMS: A hallmark of inflammatory bowel disease [IBD] is chronic inflammation, which leads to excessive extracellular matrix [ECM] remodelling and release of specific protein fragments, called neoepitopes. We speculated that the biomarker profile panel for ulcerative colitis [UC] and Crohn's disease [CD] represent a heterogeneous expression pattern, and may be applied as a tool to aid in the differentiation between UC and CD.

METHODS: Serum biomarkers of degraded collagens I, III-IV [C1M, C3M, and C4M], collagen type 1 and IV formation [P1NP, P4NP], and citrullinated and MMP-degraded vimentin [VICM] were studied with a competitive ELISA assay system in a cohort including 164 subjects [CD n = 72, UC n = 60, and non-IBD controls n = 32] and a validation cohort of 61 subjects [CD n = 46, and UC n = 15]. Receiver operating characteristic curve analysis and logistic regression modelling were carried out to evaluate the discriminative power of the biomarkers.

RESULTS: All biomarkers were corrected for confounding factors. VICM and C3M demonstrated the highest diagnostic power, alone, to differentiate CD from UC with an area under the curve [AUC] of 0.77 and 0.69, respectively. Furthermore, the biomarkers C1M [AUC = 0.81], C3M [AUC = 0.83], VICM [AUC = 0.83], and P1NP [AUC = 0.77] were best to differentiate UC from non-IBD. The best combinations of biomarkers to differentiate CD from UC and UC from non-IBD were VICM, C3M, C4M [AUC = 0.90] and VICM, C3M [AUC = 0.98] respectively.

CONCLUSIONS: Specific extracellular matrix degradation markers are elevated in IBD and can discriminate CD from UC and UC from non-IBD controls with a high diagnostic accuracy.

Original languageEnglish
JournalJournal of Crohn's and Colitis
Volume9
Issue number10
Pages (from-to)863 - 872
ISSN1873-9946
DOIs
Publication statusPublished - 18. Jul 2015

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Collagen Type III
Vimentin
Matrix Metalloproteinases
Ulcerative Colitis
Crohn Disease
Area Under Curve
Inflammatory Bowel Diseases
Collagen Type I
ROC Curve
Logistic Models

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Mortensen, Joachim Høg ; Godskesen, Line Elbjerg ; Jensen, Michael Dam ; Van Haaften, Wouter Tobias ; Klinge, Lone Gabriels ; Olinga, Peter ; Dijkstra, Gerard ; Kjeldsen, Jens ; Karsdal, Morten Asser ; Bay-Jensen, Anne-Christine ; Krag, Aleksander. / Fragments of Citrullinated and MMP-degraded Vimentin and MMP-degraded Type III Collagen Are Novel Serological Biomarkers to Differentiate Crohn's Disease from Ulcerative Colitis. In: Journal of Crohn's and Colitis. 2015 ; Vol. 9, No. 10. pp. 863 - 872.
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title = "Fragments of Citrullinated and MMP-degraded Vimentin and MMP-degraded Type III Collagen Are Novel Serological Biomarkers to Differentiate Crohn's Disease from Ulcerative Colitis",
abstract = "BACKGROUND AND AIMS: A hallmark of inflammatory bowel disease [IBD] is chronic inflammation, which leads to excessive extracellular matrix [ECM] remodelling and release of specific protein fragments, called neoepitopes. We speculated that the biomarker profile panel for ulcerative colitis [UC] and Crohn's disease [CD] represent a heterogeneous expression pattern, and may be applied as a tool to aid in the differentiation between UC and CD.METHODS: Serum biomarkers of degraded collagens I, III-IV [C1M, C3M, and C4M], collagen type 1 and IV formation [P1NP, P4NP], and citrullinated and MMP-degraded vimentin [VICM] were studied with a competitive ELISA assay system in a cohort including 164 subjects [CD n = 72, UC n = 60, and non-IBD controls n = 32] and a validation cohort of 61 subjects [CD n = 46, and UC n = 15]. Receiver operating characteristic curve analysis and logistic regression modelling were carried out to evaluate the discriminative power of the biomarkers.RESULTS: All biomarkers were corrected for confounding factors. VICM and C3M demonstrated the highest diagnostic power, alone, to differentiate CD from UC with an area under the curve [AUC] of 0.77 and 0.69, respectively. Furthermore, the biomarkers C1M [AUC = 0.81], C3M [AUC = 0.83], VICM [AUC = 0.83], and P1NP [AUC = 0.77] were best to differentiate UC from non-IBD. The best combinations of biomarkers to differentiate CD from UC and UC from non-IBD were VICM, C3M, C4M [AUC = 0.90] and VICM, C3M [AUC = 0.98] respectively.CONCLUSIONS: Specific extracellular matrix degradation markers are elevated in IBD and can discriminate CD from UC and UC from non-IBD controls with a high diagnostic accuracy.",
author = "Mortensen, {Joachim H{\o}g} and Godskesen, {Line Elbjerg} and Jensen, {Michael Dam} and {Van Haaften}, {Wouter Tobias} and Klinge, {Lone Gabriels} and Peter Olinga and Gerard Dijkstra and Jens Kjeldsen and Karsdal, {Morten Asser} and Anne-Christine Bay-Jensen and Aleksander Krag",
note = "Copyright {\circledC} 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.",
year = "2015",
month = "7",
day = "18",
doi = "10.1093/ecco-jcc/jjv123",
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Fragments of Citrullinated and MMP-degraded Vimentin and MMP-degraded Type III Collagen Are Novel Serological Biomarkers to Differentiate Crohn's Disease from Ulcerative Colitis. / Mortensen, Joachim Høg; Godskesen, Line Elbjerg; Jensen, Michael Dam; Van Haaften, Wouter Tobias; Klinge, Lone Gabriels; Olinga, Peter; Dijkstra, Gerard; Kjeldsen, Jens; Karsdal, Morten Asser; Bay-Jensen, Anne-Christine; Krag, Aleksander.

In: Journal of Crohn's and Colitis, Vol. 9, No. 10, 18.07.2015, p. 863 - 872.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Fragments of Citrullinated and MMP-degraded Vimentin and MMP-degraded Type III Collagen Are Novel Serological Biomarkers to Differentiate Crohn's Disease from Ulcerative Colitis

AU - Mortensen, Joachim Høg

AU - Godskesen, Line Elbjerg

AU - Jensen, Michael Dam

AU - Van Haaften, Wouter Tobias

AU - Klinge, Lone Gabriels

AU - Olinga, Peter

AU - Dijkstra, Gerard

AU - Kjeldsen, Jens

AU - Karsdal, Morten Asser

AU - Bay-Jensen, Anne-Christine

AU - Krag, Aleksander

N1 - Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

PY - 2015/7/18

Y1 - 2015/7/18

N2 - BACKGROUND AND AIMS: A hallmark of inflammatory bowel disease [IBD] is chronic inflammation, which leads to excessive extracellular matrix [ECM] remodelling and release of specific protein fragments, called neoepitopes. We speculated that the biomarker profile panel for ulcerative colitis [UC] and Crohn's disease [CD] represent a heterogeneous expression pattern, and may be applied as a tool to aid in the differentiation between UC and CD.METHODS: Serum biomarkers of degraded collagens I, III-IV [C1M, C3M, and C4M], collagen type 1 and IV formation [P1NP, P4NP], and citrullinated and MMP-degraded vimentin [VICM] were studied with a competitive ELISA assay system in a cohort including 164 subjects [CD n = 72, UC n = 60, and non-IBD controls n = 32] and a validation cohort of 61 subjects [CD n = 46, and UC n = 15]. Receiver operating characteristic curve analysis and logistic regression modelling were carried out to evaluate the discriminative power of the biomarkers.RESULTS: All biomarkers were corrected for confounding factors. VICM and C3M demonstrated the highest diagnostic power, alone, to differentiate CD from UC with an area under the curve [AUC] of 0.77 and 0.69, respectively. Furthermore, the biomarkers C1M [AUC = 0.81], C3M [AUC = 0.83], VICM [AUC = 0.83], and P1NP [AUC = 0.77] were best to differentiate UC from non-IBD. The best combinations of biomarkers to differentiate CD from UC and UC from non-IBD were VICM, C3M, C4M [AUC = 0.90] and VICM, C3M [AUC = 0.98] respectively.CONCLUSIONS: Specific extracellular matrix degradation markers are elevated in IBD and can discriminate CD from UC and UC from non-IBD controls with a high diagnostic accuracy.

AB - BACKGROUND AND AIMS: A hallmark of inflammatory bowel disease [IBD] is chronic inflammation, which leads to excessive extracellular matrix [ECM] remodelling and release of specific protein fragments, called neoepitopes. We speculated that the biomarker profile panel for ulcerative colitis [UC] and Crohn's disease [CD] represent a heterogeneous expression pattern, and may be applied as a tool to aid in the differentiation between UC and CD.METHODS: Serum biomarkers of degraded collagens I, III-IV [C1M, C3M, and C4M], collagen type 1 and IV formation [P1NP, P4NP], and citrullinated and MMP-degraded vimentin [VICM] were studied with a competitive ELISA assay system in a cohort including 164 subjects [CD n = 72, UC n = 60, and non-IBD controls n = 32] and a validation cohort of 61 subjects [CD n = 46, and UC n = 15]. Receiver operating characteristic curve analysis and logistic regression modelling were carried out to evaluate the discriminative power of the biomarkers.RESULTS: All biomarkers were corrected for confounding factors. VICM and C3M demonstrated the highest diagnostic power, alone, to differentiate CD from UC with an area under the curve [AUC] of 0.77 and 0.69, respectively. Furthermore, the biomarkers C1M [AUC = 0.81], C3M [AUC = 0.83], VICM [AUC = 0.83], and P1NP [AUC = 0.77] were best to differentiate UC from non-IBD. The best combinations of biomarkers to differentiate CD from UC and UC from non-IBD were VICM, C3M, C4M [AUC = 0.90] and VICM, C3M [AUC = 0.98] respectively.CONCLUSIONS: Specific extracellular matrix degradation markers are elevated in IBD and can discriminate CD from UC and UC from non-IBD controls with a high diagnostic accuracy.

U2 - 10.1093/ecco-jcc/jjv123

DO - 10.1093/ecco-jcc/jjv123

M3 - Journal article

C2 - 26188349

VL - 9

SP - 863

EP - 872

JO - Journal of Crohn's and Colitis

JF - Journal of Crohn's and Colitis

SN - 1873-9946

IS - 10

ER -