Biomarkers of collagen synthesis predict progression in the PROFILE idiopathic pulmonary fibrosis cohort
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Abstract
Idiopathic pulmonary fibrosis (IPF) is characterised by excessive extracellular matrix (ECM) deposition and remodelling. Measuring this activity provides an opportunity to develop tools capable of identifying individuals at-risk of progression. Longitudinal change in markers of ECM synthesis was assessed in 145 newly-diagnosed individuals with IPF.Serum levels of collagen synthesis neoepitopes, PRO-C3 and PRO-C6 (collagen type 3 and 6), were elevated in IPF compared with controls at baseline, and progressive disease versus stable disease during follow up, (PRO-C3 p < 0.001; PRO-C6 p = 0.029). Assessment of rate of change in neoepitope levels from baseline to 3 months (defined as 'slope to month 3': HIGH slope, slope > 0 vs. LOW slope, slope < =0) demonstrated no relationship with mortality for these markers (PRO-C3 (HR 1.62, p = 0.080); PINP (HR 0.76, p = 0.309); PRO-C6 (HR 1.14, p = 0.628)). As previously reported, rising concentrations of collagen degradation markers C1M, C3M, C6M and CRPM were associated with an increased risk of overall mortality (HR = 1.84, CI 1.03-3.27, p = 0.038, HR = 2.44, CI 1.39-4.31, p = 0.002; HR = 2.19, CI 1.25-3.82, p = 0.006; HR = 2.13 CI 1.21-3.75, p = 0.009 respectively).Elevated levels of PRO-C3 and PRO-C6 associate with IPF disease progression. Collagen synthesis and degradation biomarkers have the potential to enhance clinical trials in IPF and may inform prognostic assessment and therapeutic decision making in the clinic.
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Markers of collagen type 3 (PRO-C3) and 6 (PRO-C6) synthesis were elevated in IPF compared with healthy controls at baseline, and in progressive versus stable disease.
“Markers of collagen type 3 (PRO-C3) and 6 (PRO-C6) synthesis were also elevated in IPF compared with healthy controls at baseline, and in progressive versus stable disease (Organ et al., 2019).”
From Pulmonary fibrosis: Emerging diagnostic and therapeutic strategies (2023) · cites this paper as Organ et al., 2019
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- Authors
- Organ, L. A., Duggan, A.-M. R., Oballa, E., Taggart, S. C., Simpson, J. K., Kang’ombe, A. R., Braybrooke, R., Molyneaux, P. L., North, B., Karkera, Y., Leeming, D. J., Karsdal, M. A., Nanthakumar, C. B., Fahy, W. A., Marshall, R. P., Jenkins, R. G., & Maher, T. M.
- Affiliations
- University of Nottingham (GB)
- GlaxoSmithKline (United Kingdom) (GB)
- Royal Brompton Hospital (GB)
- Nordic Bioscience (Denmark) (DK)
- Corresponding author
- Maher, Toby M.
- ORCID
- Venue
- Respiratory Research
- Published
- 2019-07-12
- Volume
- 20
- Issue
- 1
- Pages
- 148-148
- ISSN
- 1465-9921 (ISSN-L)
- 1465-993X
- PMC
- PMC6624898
- OpenAlex
- W2959512696
- Cited by
- 139
- References
- 34
- Citations by year
- 2026: 10 · 2025: 23 · 2024: 22 · 2023: 22 · 2022: 19 · 2021: 29 · 2020: 12 · 2019: 2
- FWCI
- 11.40
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Respiratory Research (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Spiral (Imperial College London) (submittedVersion, other-oa)
- Funders
- Medical Research Council (G0901226)
- National Institute for Health Research (CS-2013-13-017)
- British Lung Foundation (C17-3)
- GlaxoSmithKline (CRT114316)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Occupational and environmental lung diseases
- Keywords
- idiopathic pulmonary fibrosis, type III collagen, PRO-C3, PRO-C6, neoantigens, extracellular matrix deposition, disease progression, mortality risk, prognostic factors
- MeSH terms
- Aged, Aged, 80 and over, Collagen, Humans, Longitudinal Studies, Middle Aged, Predictive Value of Tests, Prospective Studies, Protein Biosynthesis, Cohort Studies, Biomarkers, Disease Progression, Idiopathic Pulmonary Fibrosis
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