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

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

doi:10.1093/ecco-jcc/jjae077

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

J Crohns Colitis. 2024 May 17:jjae077. doi: 10.1093/ecco-jcc/jjae077. Online ahead of print.

Authors

Anja Poulsen^{1

2}, Pernille Dige Ovesen³, Cathy Lu⁴, Dominik Bettenworth^{5

6}, Vipul Jairath^{7

8}, Brian G Feagan^{7

8

9}, Jakob Benedict Seidelin^{2

3}, Florian Rieder^{10

11}

Affiliations

¹ Digestive Disease Center, Bispebjerg Hospital, University of Copenhagen, Copenhagen NV, Denmark.
² Department of Clinical Medicine, University of Copenhagen, Denmark.
³ Department of Gastroenterology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
⁴ Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
⁵ Medical faculty, University of Münster, Münster, Germany.
⁶ CED Schwerpunktpraxis, Münster, Germany.
⁷ Division of Gastroenterology, Department of Medicine, Western University, 1151 Richmond St, London, ON, N6A 3K7, Canada.
⁸ Department of Epidemiology and Biostatistics, Western University, 1151 Richmond St, London, ON.
⁹ Alimentiv Inc, 100 Dundas St Suite 200, London, ON, N6A 5B6, Canada.3K7, Canada.
¹⁰ 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.
¹¹ Program for Global Translational Inflammatory Bowel Diseases, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.

PMID: 38758527
DOI: 10.1093/ecco-jcc/jjae077

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 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 these 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 curves 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 remodeling and fibrosis burden, warranting further investigation.

Keywords: Biomarker; Extracellular Matrix; Inflammatory Bowel Disease.

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