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Poster presentations: Basic Science 2020

P101 Biomarkers of elastin degradation are associated with clinical and biochemically active disease in Crohn’s disease

M. Pehrsson1, V. Domislović2, M.A. Karsdal1, M. Brinar2, A. Barisic3, Z. Krznaric2, T. Manon-Jensen1, J.H. Mortensen1

1Nordic Bioscience A/S, Biomarkers and Research, Herlev, Denmark, 2University Hospital Centre Zagreb, Department of Gastroenterology and Hepatology, Zagreb, Croatia, 3University Hospital Centre Zagreb, Department for Clinical Nutrition, Zagreb, Croatia

Background

In Crohn’s disease (CD), the extensive and potentially transmural inflammation results in increased activity of both matrix metalloproteases (MMPs) and serine proteases, causing a higher degree of intestinal tissue remodelling. This increased proteolytic activity could potentially cause degradation and loss of function of mechanical and functional matrix proteins, such as elastin. Therefore, we sought to investigate the association between biomarkers of elastin degradation and the disease activity in CD patients.

Methods

Seventy-two CD patients and 29 healthy donors (HD) were included in the study. Disease activity was determined according to the Crohn’s disease activity index score (CDAI >150) and/or a faecal calprotectin (fCALP >250). Additionally, CD patients were endoscopically assessed according to the simple endoscopic score (SES) for CD. Different protease derived biomarkers of elastin degradation: protease-3 (ELP-3), MMP-7 (ELM-7) and cathepsin-G (EL-CG) was measured in serum by ELISA. One-way ANOVA (Kruskal–Wallis) was applied for the statistical analysis.

Results

The levels of ELP-3 was significantly elevated in active CD when compared with the HD (p < 0.001), and inactive CD (p < 0.01). Levels of EL-G were significantly elevated when comparing active CD and HD (p < 0.05), with the same result observed for the levels of EL-CG when comparing active CD and the HD (p < 0.05). Endoscopically, ELP-3 was shown significantly elevated in moderate–to-severe CD patients when compared with the HD (p < 0.01).

Figure 1. Depicts the levels of the elastin degradation markers in CD, and the differences between HD and CD patients with either inactive or active disease based on a CDAI >150 and/or fCALP >250. The lower part of the figure depicts the levels of ELP-3 in CD, and the differences between HD and CD patients in remission, with mild, or moderate-to-severe CD based on their SES score. Significance illustrated as follows: p < 0.05 *, p < 0.01 **, and p < 0.001 ***.

Conclusion

In this study, measurements of the elastin degradation markers were capable of differentiating between CD patients with either a clinically active or biochemically active disease, with the biomarker levels being significantly highest in the patients with an active disease. This was also the case when assessing endoscopic disease activity, where the protease-3-derived biomarker levels were highest in patients of moderate-to-severe disease activity. As such, the data provide indications of the beneficial use of these serum biomarkers as additional disease activity assessment tools for CD patients.