Endotrophin and C6Ma3, serological biomarkers of type VI collagen remodelling, reflect endoscopic and clinical disease activity in IBD

Abstract In inflammatory bowel disease (IBD), the chronic inflammation deeply affects the intestinal extracellular matrix. The aim of this study was to investigate if remodeling of the intestinal basement membrane type VI collagen was associated with pathophysiological changes in Crohn’s disease (CD...

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Autores principales:	Majken Lindholm, Line E. Godskesen, Tina Manon-Jensen, Jens Kjeldsen, Aleksander Krag, Morten A. Karsdal, Joachim H. Mortensen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/972d3bdc2a5b456d8909432fa73adc04
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spelling	oai:doaj.org-article:972d3bdc2a5b456d8909432fa73adc042021-12-02T16:26:30ZEndotrophin and C6Ma3, serological biomarkers of type VI collagen remodelling, reflect endoscopic and clinical disease activity in IBD10.1038/s41598-021-94321-22045-2322https://doaj.org/article/972d3bdc2a5b456d8909432fa73adc042021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94321-2https://doaj.org/toc/2045-2322Abstract In inflammatory bowel disease (IBD), the chronic inflammation deeply affects the intestinal extracellular matrix. The aim of this study was to investigate if remodeling of the intestinal basement membrane type VI collagen was associated with pathophysiological changes in Crohn’s disease (CD) and ulcerative colitis (UC). Serum from IBD patients (CD: n = 65; UC: n = 107; irritable bowel syndrome: n = 18; healthy subjects: n = 20) was investigated in this study. The serological biomarkers C6Ma3 (a matrix metalloproteinase (MMP) generated fragment of the type VI collagen α3 chain) and PRO-C6, also called endotrophin (the C-terminus of the released C5 domain of the type VI collagen α3 chain) were measured by ELISAs. Serum C6Ma3 was increased in CD patients with moderate to severe and mild endoscopically active disease compared to endoscopic remission (p = 0.002, p = 0.0048), respectively, and could distinguish endoscopically active disease from remission with an AUC of 1.0 (sensitivity: 100%, specificity: 100%) (p < 0.0001), which was superior to CRP. C6Ma3 was increased in CD patients with moderate to severe clinical disease compared to mild and remission (p = 0.04; p = 0.009). Serum PRO-C6, endotrophin, was increased in CD patients in clinically remission compared to mild disease (p = 0.04) and moderate to severe disease (p = 0.065). In UC, fecal calprotectin was the only marker that alone could distinguish both clinical and endoscopic active and inactive disease. Type VI collagen degradation of the α3 chain mediated by MMPs was increased in CD patients with endoscopically active disease, measured by the serological biomarker C6Ma3, which was able to distinguish endoscopically active from inactive CD.Majken LindholmLine E. GodskesenTina Manon-JensenJens KjeldsenAleksander KragMorten A. KarsdalJoachim H. MortensenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Majken Lindholm Line E. Godskesen Tina Manon-Jensen Jens Kjeldsen Aleksander Krag Morten A. Karsdal Joachim H. Mortensen Endotrophin and C6Ma3, serological biomarkers of type VI collagen remodelling, reflect endoscopic and clinical disease activity in IBD
description	Abstract In inflammatory bowel disease (IBD), the chronic inflammation deeply affects the intestinal extracellular matrix. The aim of this study was to investigate if remodeling of the intestinal basement membrane type VI collagen was associated with pathophysiological changes in Crohn’s disease (CD) and ulcerative colitis (UC). Serum from IBD patients (CD: n = 65; UC: n = 107; irritable bowel syndrome: n = 18; healthy subjects: n = 20) was investigated in this study. The serological biomarkers C6Ma3 (a matrix metalloproteinase (MMP) generated fragment of the type VI collagen α3 chain) and PRO-C6, also called endotrophin (the C-terminus of the released C5 domain of the type VI collagen α3 chain) were measured by ELISAs. Serum C6Ma3 was increased in CD patients with moderate to severe and mild endoscopically active disease compared to endoscopic remission (p = 0.002, p = 0.0048), respectively, and could distinguish endoscopically active disease from remission with an AUC of 1.0 (sensitivity: 100%, specificity: 100%) (p < 0.0001), which was superior to CRP. C6Ma3 was increased in CD patients with moderate to severe clinical disease compared to mild and remission (p = 0.04; p = 0.009). Serum PRO-C6, endotrophin, was increased in CD patients in clinically remission compared to mild disease (p = 0.04) and moderate to severe disease (p = 0.065). In UC, fecal calprotectin was the only marker that alone could distinguish both clinical and endoscopic active and inactive disease. Type VI collagen degradation of the α3 chain mediated by MMPs was increased in CD patients with endoscopically active disease, measured by the serological biomarker C6Ma3, which was able to distinguish endoscopically active from inactive CD.
format	article
author	Majken Lindholm Line E. Godskesen Tina Manon-Jensen Jens Kjeldsen Aleksander Krag Morten A. Karsdal Joachim H. Mortensen
author_facet	Majken Lindholm Line E. Godskesen Tina Manon-Jensen Jens Kjeldsen Aleksander Krag Morten A. Karsdal Joachim H. Mortensen
author_sort	Majken Lindholm
title	Endotrophin and C6Ma3, serological biomarkers of type VI collagen remodelling, reflect endoscopic and clinical disease activity in IBD
title_short	Endotrophin and C6Ma3, serological biomarkers of type VI collagen remodelling, reflect endoscopic and clinical disease activity in IBD
title_full	Endotrophin and C6Ma3, serological biomarkers of type VI collagen remodelling, reflect endoscopic and clinical disease activity in IBD
title_fullStr	Endotrophin and C6Ma3, serological biomarkers of type VI collagen remodelling, reflect endoscopic and clinical disease activity in IBD
title_full_unstemmed	Endotrophin and C6Ma3, serological biomarkers of type VI collagen remodelling, reflect endoscopic and clinical disease activity in IBD
title_sort	endotrophin and c6ma3, serological biomarkers of type vi collagen remodelling, reflect endoscopic and clinical disease activity in ibd
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/972d3bdc2a5b456d8909432fa73adc04
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Endotrophin and C6Ma3, serological biomarkers of type VI collagen remodelling, reflect endoscopic and clinical disease activity in IBD

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