Serological Assessment of the Quality of Wound Healing Processes in Crohn's Disease

Shu Sun, Morten Asser Karsdal, Joachim Høg Mortensen, Yunyun Luo, Jens Kjeldsen, Aleksander Krag, Michael Dam Jensen, Anne Christine Bay-Jensen, Tina Manon-Jensen

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

BACKGROUND AND AIMS: Crohn's disease (CD) is a chronic inflammatory condition characterized by continuous mucosal damage and ongoing wound healing of the intestines. The fibrinolytic system is involved in early parts of the wound healing process. Fibrin is a key mediator of primary blood clot formation and is formed by cross-linking of fibrinogen. To gain insights into the dynamics of wound healing in CD patients we investigated the conversion of fibrinogen into fibrin by the pro-peptide FPA, the amount of factor XIII cross-linked fibrin and total fibrin clot. METHODS: Serum samples of 35 CD patients, 15 non-inflammatory bowel disease (non-IBD) patients and 39 age-matched healthy controls were analyzed for three novel neo-epitope markers: D-fragment and D-dimer, reflecting the degradation of total fibrin clot and factor XIII cross-linked fibrin, as well as FPA, reflecting synthesis of fibrin. RESULTS: Crohn's disease patients had a significantly lower D-dimer level (p=0.0001) compared to healthy controls. Crohn's disease and non-IBD patients had a significantly higher level of FPA (p<0.0001) and D-fragment/D-dimer ratio (p<0.0001 and p=0.02). FPA, D-dimer and D-fragment/D-dimer ratio could distinguish CD patients from healthy controls with area under the curve of 0.92 (95% CI 0.83-0.97), 0.78 (95% CI 0.67-0.87) and 0.85 (95% CI 0.75-0.93), respectively. CONCLUSION: Wound healing parameters were clearly changed in CD patients. FPA levels were higher in CD patients as compared to healthy controls, indicating more ongoing wound healing. D-dimer levels were lower in CD patients than in healthy controls, indicating impaired wound healing due to poor quality of factor XIII cross-linked fibrin and clot resolution.

Original languageEnglish
JournalJournal of gastrointestinal and liver diseases : JGLD
Volume28
Issue number2
Pages (from-to)175-182
ISSN1841-8724
DOIs
Publication statusPublished - 1. Jun 2019

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Crohn Disease
Area Under Curve
Intestines
Peptides
Serum

Keywords

  • Crohn’s disease
  • D-dimer
  • Fibrin
  • Fibrinogen
  • Fibrinopeptide A

Cite this

Sun, Shu ; Karsdal, Morten Asser ; Mortensen, Joachim Høg ; Luo, Yunyun ; Kjeldsen, Jens ; Krag, Aleksander ; Jensen, Michael Dam ; Bay-Jensen, Anne Christine ; Manon-Jensen, Tina. / Serological Assessment of the Quality of Wound Healing Processes in Crohn's Disease. In: Journal of gastrointestinal and liver diseases : JGLD. 2019 ; Vol. 28, No. 2. pp. 175-182.
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title = "Serological Assessment of the Quality of Wound Healing Processes in Crohn's Disease",
abstract = "BACKGROUND AND AIMS: Crohn's disease (CD) is a chronic inflammatory condition characterized by continuous mucosal damage and ongoing wound healing of the intestines. The fibrinolytic system is involved in early parts of the wound healing process. Fibrin is a key mediator of primary blood clot formation and is formed by cross-linking of fibrinogen. To gain insights into the dynamics of wound healing in CD patients we investigated the conversion of fibrinogen into fibrin by the pro-peptide FPA, the amount of factor XIII cross-linked fibrin and total fibrin clot. METHODS: Serum samples of 35 CD patients, 15 non-inflammatory bowel disease (non-IBD) patients and 39 age-matched healthy controls were analyzed for three novel neo-epitope markers: D-fragment and D-dimer, reflecting the degradation of total fibrin clot and factor XIII cross-linked fibrin, as well as FPA, reflecting synthesis of fibrin. RESULTS: Crohn's disease patients had a significantly lower D-dimer level (p=0.0001) compared to healthy controls. Crohn's disease and non-IBD patients had a significantly higher level of FPA (p<0.0001) and D-fragment/D-dimer ratio (p<0.0001 and p=0.02). FPA, D-dimer and D-fragment/D-dimer ratio could distinguish CD patients from healthy controls with area under the curve of 0.92 (95{\%} CI 0.83-0.97), 0.78 (95{\%} CI 0.67-0.87) and 0.85 (95{\%} CI 0.75-0.93), respectively. CONCLUSION: Wound healing parameters were clearly changed in CD patients. FPA levels were higher in CD patients as compared to healthy controls, indicating more ongoing wound healing. D-dimer levels were lower in CD patients than in healthy controls, indicating impaired wound healing due to poor quality of factor XIII cross-linked fibrin and clot resolution.",
keywords = "Crohn’s disease, D-dimer, Fibrin, Fibrinogen, Fibrinopeptide A",
author = "Shu Sun and Karsdal, {Morten Asser} and Mortensen, {Joachim H{\o}g} and Yunyun Luo and Jens Kjeldsen and Aleksander Krag and Jensen, {Michael Dam} and Bay-Jensen, {Anne Christine} and Tina Manon-Jensen",
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Serological Assessment of the Quality of Wound Healing Processes in Crohn's Disease. / Sun, Shu; Karsdal, Morten Asser; Mortensen, Joachim Høg; Luo, Yunyun; Kjeldsen, Jens; Krag, Aleksander; Jensen, Michael Dam; Bay-Jensen, Anne Christine; Manon-Jensen, Tina.

In: Journal of gastrointestinal and liver diseases : JGLD, Vol. 28, No. 2, 01.06.2019, p. 175-182.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Serological Assessment of the Quality of Wound Healing Processes in Crohn's Disease

AU - Sun, Shu

AU - Karsdal, Morten Asser

AU - Mortensen, Joachim Høg

AU - Luo, Yunyun

AU - Kjeldsen, Jens

AU - Krag, Aleksander

AU - Jensen, Michael Dam

AU - Bay-Jensen, Anne Christine

AU - Manon-Jensen, Tina

PY - 2019/6/1

Y1 - 2019/6/1

N2 - BACKGROUND AND AIMS: Crohn's disease (CD) is a chronic inflammatory condition characterized by continuous mucosal damage and ongoing wound healing of the intestines. The fibrinolytic system is involved in early parts of the wound healing process. Fibrin is a key mediator of primary blood clot formation and is formed by cross-linking of fibrinogen. To gain insights into the dynamics of wound healing in CD patients we investigated the conversion of fibrinogen into fibrin by the pro-peptide FPA, the amount of factor XIII cross-linked fibrin and total fibrin clot. METHODS: Serum samples of 35 CD patients, 15 non-inflammatory bowel disease (non-IBD) patients and 39 age-matched healthy controls were analyzed for three novel neo-epitope markers: D-fragment and D-dimer, reflecting the degradation of total fibrin clot and factor XIII cross-linked fibrin, as well as FPA, reflecting synthesis of fibrin. RESULTS: Crohn's disease patients had a significantly lower D-dimer level (p=0.0001) compared to healthy controls. Crohn's disease and non-IBD patients had a significantly higher level of FPA (p<0.0001) and D-fragment/D-dimer ratio (p<0.0001 and p=0.02). FPA, D-dimer and D-fragment/D-dimer ratio could distinguish CD patients from healthy controls with area under the curve of 0.92 (95% CI 0.83-0.97), 0.78 (95% CI 0.67-0.87) and 0.85 (95% CI 0.75-0.93), respectively. CONCLUSION: Wound healing parameters were clearly changed in CD patients. FPA levels were higher in CD patients as compared to healthy controls, indicating more ongoing wound healing. D-dimer levels were lower in CD patients than in healthy controls, indicating impaired wound healing due to poor quality of factor XIII cross-linked fibrin and clot resolution.

AB - BACKGROUND AND AIMS: Crohn's disease (CD) is a chronic inflammatory condition characterized by continuous mucosal damage and ongoing wound healing of the intestines. The fibrinolytic system is involved in early parts of the wound healing process. Fibrin is a key mediator of primary blood clot formation and is formed by cross-linking of fibrinogen. To gain insights into the dynamics of wound healing in CD patients we investigated the conversion of fibrinogen into fibrin by the pro-peptide FPA, the amount of factor XIII cross-linked fibrin and total fibrin clot. METHODS: Serum samples of 35 CD patients, 15 non-inflammatory bowel disease (non-IBD) patients and 39 age-matched healthy controls were analyzed for three novel neo-epitope markers: D-fragment and D-dimer, reflecting the degradation of total fibrin clot and factor XIII cross-linked fibrin, as well as FPA, reflecting synthesis of fibrin. RESULTS: Crohn's disease patients had a significantly lower D-dimer level (p=0.0001) compared to healthy controls. Crohn's disease and non-IBD patients had a significantly higher level of FPA (p<0.0001) and D-fragment/D-dimer ratio (p<0.0001 and p=0.02). FPA, D-dimer and D-fragment/D-dimer ratio could distinguish CD patients from healthy controls with area under the curve of 0.92 (95% CI 0.83-0.97), 0.78 (95% CI 0.67-0.87) and 0.85 (95% CI 0.75-0.93), respectively. CONCLUSION: Wound healing parameters were clearly changed in CD patients. FPA levels were higher in CD patients as compared to healthy controls, indicating more ongoing wound healing. D-dimer levels were lower in CD patients than in healthy controls, indicating impaired wound healing due to poor quality of factor XIII cross-linked fibrin and clot resolution.

KW - Crohn’s disease

KW - D-dimer

KW - Fibrin

KW - Fibrinogen

KW - Fibrinopeptide A

U2 - 10.15403/jgld-178

DO - 10.15403/jgld-178

M3 - Journal article

C2 - 31204415

AN - SCOPUS:85068210597

VL - 28

SP - 175

EP - 182

JO - Journal of Gastrointestinal and Liver Diseases

JF - Journal of Gastrointestinal and Liver Diseases

SN - 1841-8724

IS - 2

ER -