Serological biomarkers of type I, III and IV collagen turnover are associated with the presence and future progression of stricturing and penetrating Crohn's disease.
Journal
Alimentary pharmacology & therapeutics
ISSN: 1365-2036
Titre abrégé: Aliment Pharmacol Ther
Pays: England
ID NLM: 8707234
Informations de publication
Date de publication:
08 2022
08 2022
Historique:
revised:
09
03
2022
received:
04
02
2022
accepted:
18
05
2022
pubmed:
7
6
2022
medline:
28
7
2022
entrez:
6
6
2022
Statut:
ppublish
Résumé
Increased collagen remodelling is a key pathophysiological component underlying intestinal stricture and fistula development in Crohn's disease (CD). To investigate associations between serological biomarkers of collagen turnover and disease behaviour according to the Montreal classification in patients with CD. Serological biomarkers of type III/IV collagen formation (PRO-C3, PRO-C4) and matrix metalloproteinase (MMP) or granzyme-B (GrzB)-mediated type I, III, IV and VI collagen degradation (C1M, C3M, C4M, C4G, C6Ma3) were measured using neo-epitope protein fingerprint assays in 101 patients with CD (Montreal B1: n = 37; B2: n = 27; B3: n = 37) and 96 controls. Patients were followed up until their last outpatient visit to monitor stricturing/penetrating disease progression and recurrence and the occurrence of surgical interventions. C1M, C3M and C4M were significantly reduced in patients with stricturing disease (Montreal B2) and accurately differentiated them from patients with either non-stricturing, non-penetrating (B1) or penetrating (B3) disease (all p < 0.001, multivariable analysis). Similarly, the type IV collagen formation/degradation (PRO-C4/C4M) ratio demonstrated high discriminative capacity (B1/B2: AUC = 0.90; B1/B3: AUC = 0.87, both p < 0.001, multivariable analysis). Prospectively, higher baseline levels of C1M and C4G were associated with an increased risk of penetrating disease progression (C4G: hazard ratio [HR] 1.71 [1.05-2.81], p < 0.05). Elevated degradation of type I, III and IV collagen and excessive (relative) formation of type IV collagen strongly associates with stricturing CD. Type I and IV collagen fragments show predictive potential for the risk of penetrating disease progression. These biomarkers may become valuable tools for detection and prediction of stricturing and penetrating CD.
Sections du résumé
BACKGROUND
Increased collagen remodelling is a key pathophysiological component underlying intestinal stricture and fistula development in Crohn's disease (CD).
AIMS
To investigate associations between serological biomarkers of collagen turnover and disease behaviour according to the Montreal classification in patients with CD.
METHODS
Serological biomarkers of type III/IV collagen formation (PRO-C3, PRO-C4) and matrix metalloproteinase (MMP) or granzyme-B (GrzB)-mediated type I, III, IV and VI collagen degradation (C1M, C3M, C4M, C4G, C6Ma3) were measured using neo-epitope protein fingerprint assays in 101 patients with CD (Montreal B1: n = 37; B2: n = 27; B3: n = 37) and 96 controls. Patients were followed up until their last outpatient visit to monitor stricturing/penetrating disease progression and recurrence and the occurrence of surgical interventions.
RESULTS
C1M, C3M and C4M were significantly reduced in patients with stricturing disease (Montreal B2) and accurately differentiated them from patients with either non-stricturing, non-penetrating (B1) or penetrating (B3) disease (all p < 0.001, multivariable analysis). Similarly, the type IV collagen formation/degradation (PRO-C4/C4M) ratio demonstrated high discriminative capacity (B1/B2: AUC = 0.90; B1/B3: AUC = 0.87, both p < 0.001, multivariable analysis). Prospectively, higher baseline levels of C1M and C4G were associated with an increased risk of penetrating disease progression (C4G: hazard ratio [HR] 1.71 [1.05-2.81], p < 0.05).
CONCLUSIONS
Elevated degradation of type I, III and IV collagen and excessive (relative) formation of type IV collagen strongly associates with stricturing CD. Type I and IV collagen fragments show predictive potential for the risk of penetrating disease progression. These biomarkers may become valuable tools for detection and prediction of stricturing and penetrating CD.
Identifiants
pubmed: 35661188
doi: 10.1111/apt.17063
pmc: PMC9544881
doi:
Substances chimiques
Biomarkers
0
Collagen Type I
0
Collagen Type III
0
Collagen Type IV
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
675-693Informations de copyright
© 2022 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.
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