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Misbalance in type III collagen formation/degradation as a novel serological biomarker for penetrating (Montreal B3) Crohn's disease

BACKGROUND: Misbalances in extracellular matrix turnover are key factors in the development of stricturing (Montreal B2) and penetrating (Montreal B3) Crohn's disease. AIM: To determine whether serological markers for collagen formation and degradation could serve as biomarkers for complication...

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Autores principales: van Haaften, W. T., Mortensen, J. H., Karsdal, M. A., Bay‐Jensen, A. C., Dijkstra, G., Olinga, P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6221070/
https://www.ncbi.nlm.nih.gov/pubmed/28481042
http://dx.doi.org/10.1111/apt.14092
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author van Haaften, W. T.
Mortensen, J. H.
Karsdal, M. A.
Bay‐Jensen, A. C.
Dijkstra, G.
Olinga, P.
author_facet van Haaften, W. T.
Mortensen, J. H.
Karsdal, M. A.
Bay‐Jensen, A. C.
Dijkstra, G.
Olinga, P.
author_sort van Haaften, W. T.
collection PubMed
description BACKGROUND: Misbalances in extracellular matrix turnover are key factors in the development of stricturing (Montreal B2) and penetrating (Montreal B3) Crohn's disease. AIM: To determine whether serological markers for collagen formation and degradation could serve as biomarkers for complications of Crohn's disease. METHODS: Serum biomarkers for type I, III, V and VI collagen formation (P1NP, Pro‐C3, Pro‐C5, Pro‐C6) and matrix metalloproteinase mediated degradation (C1M, C3M, C5M and C6M) were measured in a retrospective, single centre cohort of 112 patients with Crohn's disease in the terminal ileum (nonstricturing/nonpenetrating: n=40, stricturing: n=55, penetrating: n=17) and 24 healthy controls. Active inflammation was defined as CRP >5 mg/L. RESULTS: C3M and Pro‐C5 levels were higher in penetrating vs nonpenetrating/nonstricturing and stricturing disease (33.6±5 vs 25.8±2.2 [P=.004] and 27.2±2.3 [P=.018] nmol/L C3M, 1262.7±259.4 vs 902.9±109.9 [P=.005] and 953.0±106.4 [P=.015] nmol/L Pro‐C5). C1M (71.2±26.1 vs 46.2±6.2 nmol/L [P<.001]), C3M (31.6±3.9 vs 26.1±1.6 nmol/L [P=.002] and Pro‐C5 levels (1171.7±171.5 vs 909.6±80.4 nmol/L [P=.002]) were higher in patients with active inflammation vs without active inflammation. Pro‐C3/C3M‐ratios were best to differentiate between penetrating vs nonstricturing/nonpenetrating and stricturing disease with area under the curves of 0.815±0.109 (P<.001) and 0.746±0.114 (P=.002) respectively. CONCLUSIONS: Serological biomarkers show that penetrating Crohn's disease is characterised by increased matrix metalloproteinase‐9 degraded type III collagen and formation of type V collagen. Active inflammation in Crohn's disease is characterised by increased formation of type V collagen and increased matrix metalloproteinase mediated breakdown of type I, III collagen. Pro‐C3/C3M ratios are superior in differentiating between penetrating Crohn's disease vs inflammatory and stricturing Crohn's disease.
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spelling pubmed-62210702018-11-15 Misbalance in type III collagen formation/degradation as a novel serological biomarker for penetrating (Montreal B3) Crohn's disease van Haaften, W. T. Mortensen, J. H. Karsdal, M. A. Bay‐Jensen, A. C. Dijkstra, G. Olinga, P. Aliment Pharmacol Ther Novel Serological Marker for Crohn's BACKGROUND: Misbalances in extracellular matrix turnover are key factors in the development of stricturing (Montreal B2) and penetrating (Montreal B3) Crohn's disease. AIM: To determine whether serological markers for collagen formation and degradation could serve as biomarkers for complications of Crohn's disease. METHODS: Serum biomarkers for type I, III, V and VI collagen formation (P1NP, Pro‐C3, Pro‐C5, Pro‐C6) and matrix metalloproteinase mediated degradation (C1M, C3M, C5M and C6M) were measured in a retrospective, single centre cohort of 112 patients with Crohn's disease in the terminal ileum (nonstricturing/nonpenetrating: n=40, stricturing: n=55, penetrating: n=17) and 24 healthy controls. Active inflammation was defined as CRP >5 mg/L. RESULTS: C3M and Pro‐C5 levels were higher in penetrating vs nonpenetrating/nonstricturing and stricturing disease (33.6±5 vs 25.8±2.2 [P=.004] and 27.2±2.3 [P=.018] nmol/L C3M, 1262.7±259.4 vs 902.9±109.9 [P=.005] and 953.0±106.4 [P=.015] nmol/L Pro‐C5). C1M (71.2±26.1 vs 46.2±6.2 nmol/L [P<.001]), C3M (31.6±3.9 vs 26.1±1.6 nmol/L [P=.002] and Pro‐C5 levels (1171.7±171.5 vs 909.6±80.4 nmol/L [P=.002]) were higher in patients with active inflammation vs without active inflammation. Pro‐C3/C3M‐ratios were best to differentiate between penetrating vs nonstricturing/nonpenetrating and stricturing disease with area under the curves of 0.815±0.109 (P<.001) and 0.746±0.114 (P=.002) respectively. CONCLUSIONS: Serological biomarkers show that penetrating Crohn's disease is characterised by increased matrix metalloproteinase‐9 degraded type III collagen and formation of type V collagen. Active inflammation in Crohn's disease is characterised by increased formation of type V collagen and increased matrix metalloproteinase mediated breakdown of type I, III collagen. Pro‐C3/C3M ratios are superior in differentiating between penetrating Crohn's disease vs inflammatory and stricturing Crohn's disease. John Wiley and Sons Inc. 2017-05-08 2017-07 /pmc/articles/PMC6221070/ /pubmed/28481042 http://dx.doi.org/10.1111/apt.14092 Text en © 2017 The Authors. Alimentary Pharmacology and Therapeutics published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Novel Serological Marker for Crohn's
van Haaften, W. T.
Mortensen, J. H.
Karsdal, M. A.
Bay‐Jensen, A. C.
Dijkstra, G.
Olinga, P.
Misbalance in type III collagen formation/degradation as a novel serological biomarker for penetrating (Montreal B3) Crohn's disease
title Misbalance in type III collagen formation/degradation as a novel serological biomarker for penetrating (Montreal B3) Crohn's disease
title_full Misbalance in type III collagen formation/degradation as a novel serological biomarker for penetrating (Montreal B3) Crohn's disease
title_fullStr Misbalance in type III collagen formation/degradation as a novel serological biomarker for penetrating (Montreal B3) Crohn's disease
title_full_unstemmed Misbalance in type III collagen formation/degradation as a novel serological biomarker for penetrating (Montreal B3) Crohn's disease
title_short Misbalance in type III collagen formation/degradation as a novel serological biomarker for penetrating (Montreal B3) Crohn's disease
title_sort misbalance in type iii collagen formation/degradation as a novel serological biomarker for penetrating (montreal b3) crohn's disease
topic Novel Serological Marker for Crohn's
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6221070/
https://www.ncbi.nlm.nih.gov/pubmed/28481042
http://dx.doi.org/10.1111/apt.14092
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