Serum Extracellular Matrix Molecules and Their Fragments as Biomarkers of Inflammation and Fibrosis in Inflammatory Bowel Diseases: A Systematic Review.

Anja Poulsen, Dominik Bettenworth, Florian Rieder, Cathy Lu, Brian G Feagan, Vipul Jairath, Pernille Dige Ovesen, Jakob Benedict Seidelin

Journal: Journal of Crohn's & colitis 2024;18(11):1894-1934

PMID: 38758527

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Abstract

BACKGROUND AND AIM

Contemporary techniques to assess disease activity or bowel damage in patients with inflammatory bowel disease [IBD], such as endoscopy and imaging, are either invasive or lack accuracy. Non-invasive biomarkers for this purpose remain an unmet medical need. Herein, we provide a comprehensive systematic review of studies evaluating blood extracellular matrix [ECM] biomarkers and their relevance in IBD.

METHODS

We conducted a systematic review of PubMed, EMBASE, Web of Science, and Scopus to identify citations pertaining to ECM biomarkers of IBD up to March 1, 2024. Studies were categorized based on marker subtype and clinical use.

RESULTS

Thirty-one ECM markers were identified, 28 of which demonstrated the ability to differentiate IBD disease activity. Collagen III emerged as the most extensively investigated [1212 IBD patients], with the degradation marker C3M and deposition marker PRO-C3 being associated with IBD and subtypes. Collagen V markers C5M and PRO-C5 emerged as the most accurate single markers for diagnosis of IBD, with an area under the curve of 0.91 and 0.93, respectively. Overall, studies were characterized by variable endpoints. None of the studies included histological grading of intestinal damage, repair, or fibrosis formation as the primary outcome in relation to the ECM blood markers.

CONCLUSIONS

Multiple ECM markers are linked with IBD and its phenotypes. However, more rigorous study designs and clearly defined endpoints are needed to ensure reproducibility and develop reliable and accurate biomarkers. ECM markers hold promise as they provide a 'window' into transmural tissue remodelling and fibrosis burden, warranting further investigation.

© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact [email protected] for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact [email protected].

Address: Digestive Disease Center, Bispebjerg Hospital, University of Copenhagen, Copenhagen NV, Denmark.; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.; Department of Gastroenterology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.; Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada.; Medical Faculty, University of Münster, Münster, Germany.; CED Schwerpunktpraxis, Münster, Germany.; Division of Gastroenterology, Department of Medicine, Western University, London, ON N6A 3K7, Canada.; Department of Epidemiology and Biostatistics, Western University, London, ON N6A, Canada.; Division of Gastroenterology, Department of Medicine, Western University, London, ON N6A 3K7, Canada.; Department of Epidemiology and Biostatistics, Western University, London, ON N6A, Canada.; Alimentiv Inc, London, ON N6A 5B6, Canada.; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.; Department of Gastroenterology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.; Department of Inflammation and Immunity, Lerner Research Institute; Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.; Program for Global Translational Inflammatory Bowel Diseases, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.

DOI: 10.1093/ecco-jcc/jjae077

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MeSH Terms: Humans, Biomarkers, Inflammatory Bowel Diseases, Fibrosis, Extracellular Matrix, Inflammation, Extracellular Matrix Proteins