open access publication

Article, 2023

Blood-Based Biomarkers Reflecting Protease 3 and MMP-12 Catalyzed Elastin Degradation as Potential Noninvasive Surrogate Markers of Endoscopic and Clinical Disease in Inflammatory Bowel Disease

Journal of Clinical Medicine, ISSN 2077-0383, Volume 13, 1, Page 21, 10.3390/jcm13010021

Contributors

Pehrsson, Martin 0000-0002-4787-5563 (Corresponding author) [1] Domislovic, Viktor 0000-0002-3715-5730 [2] Alexdóttir, Marta Sorokina 0000-0002-7028-4307 [1] Brinar, Marko [2] Karsdal, Morten Asser 0000-0002-4764-5100 [1] Barisic, Ana Acman 0000-0001-9101-6232 [2] Krznaric, Zeljko 0000-0003-3758-4540 [2] Mortensen, Joachim Høg 0000-0003-0326-7264 [1]

Affiliations

  1. [1] Nordic Bioscience (Denmark)
  2. [NORA names: Nordic Bioscience; Private Research; Denmark; Europe, EU; Nordic; OECD];
  3. [2] University Hospital Centre Zagreb
  4. [NORA names: Croatia; Europe, EU]

Abstract

Chronic inflammation in inflammatory bowel disease (IBD) triggers significant extracellular matrix remodeling, including elastin remodeling, leading to severe clinical complications. Novel methods to assess intestinal tissue destruction may act as surrogate markers of endoscopic disease activity, relieving patients of invasive endoscopy. We explored the noninvasive blood-based biomarkers ELP-3 and ELM-12, measuring elastin degradation in IBD. In a study involving 104 Crohn's disease (CD), 39 ulcerative colitis (UC), and 29 healthy donors, we assessed these biomarkers' association with endoscopic and clinical disease activity using ELISA. Patients were evaluated based on the SES-CD and CDAI for CD patients and modified MES and partial Mayo for UC patients. ELP-3 and ELM-12 were elevated in patients with IBD. Discerning CD patients in endoscopic remission and mild from moderate to severe, ELP-3 provided an AUC of 0.69 and ELM-12 an AUC of 0.73. The ELP-3 biomarker was associated with UC patients and provided the highest diagnostic power of 0.87 for remission vs. active clinical disease. The data suggest an association of ELP-3 with active CD and ELM-12 with endoscopic remission in CD patients. Additionally, ELP-3 could identify UC patients with active clinical disease from patients in remission. The noninvasive biomarkers ELP-3 and ELM-12 could be potential surrogate biomarkers of elastin degradation and endoscopic and clinical disease markers.

Keywords

AUC, CD patients, CDAI, Crohn, Crohn's disease, ELISA, ELM-12, MES, MMP-12, Mayo, SES-CD, UC patients, active CD, active clinical disease, activity, association, biomarker associations, biomarkers, biomarkers of elastin degradation, blood-based biomarkers, bowel disease, chronic inflammation, clinical complications, clinical disease, clinical disease activity, clinical disease markers, colitis, complications, data, degradation, destruction, diagnostic power, disease, disease activity, disease markers, donor, elastin, elastin degradation, elastin remodeling, endoscopic disease activity, endoscopic remission, endoscopy, extracellular matrix remodeling, healthy donors, highest diagnostic power, inflammation, inflammatory bowel disease, invasive endoscopy, markers, matrix remodeling, method, noninvasive surrogate marker, novel method, partial Mayo, patients, power, protease, protease 3, remission, remodeling, severe clinical complications, study, surrogate biomarker, surrogate marker, tissue destruction, ulcerative colitis

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