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Poster presentations: Basic Science 2020

P047 Differences in extra cellular matrix remodelling in highly active Crohn’s disease and ulcerative colitis

V. Domislović1, J.H. Mortensen2, M.A. Karsdal2, M. Brinar1, T. Manon-Jensen2, Ž. Krznarić1

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

Background

Ulcerative colitis (UC) and Crohn’s disease (CD) require continuous evaluation of disease activity and response to therapy. Current gold standard is endoscopy; therefore it is important to investigate biomarkers associated with endoscopic disease activity. Extra cellular matrix (ECM) consists of basement membrane (BM) and interstitial matrix (IM). BM consists mainly of type IV collagen, while IM of types I, III and V collagen. Pathological environment leads to impaired remodelling, structure, quality and function of the ECM. We investigated biomarkers of collagen degradation and formation and their association with endoscopic disease activity and in patients with CD and UC.

Methods

In this cross-sectional study, we measured six biomarkers of ECM remodelling in 94 IBD patients (60 with CD and 34 UC). Biomarkers of type III collagen degradation (C3M) and formation (PRO-C3), type IV collagen degradation (C4M), formation (PRO-C4), type V collagen formation (PRO-C5) and PROC23 were measured in serum by ELISA. Inflammatory activity was measured using endoscopic scores; SES-CD for CD, MES and modified MES (mMES) for UC. Patients were divided in remission and mild activity group vs. moderate-to-severe activity (SES-CD < 3 vs. ≥3 and MES < 2 vs. ≥2) Student t-test and correlation analysis were applied in statistical analysis.

Results

CD patients with moderate and severe disease had lower levels of PRO-C3 (14.7 ± 10.5 vs. 9.9 ± 4.6, p = 0.04), and higher levels of C4M (26.54 ± 10.5 vs. 37.8 ± 20, p = 0.009) compared with patients in remission and mild disease. Biomarker of type III collagen turnover (C3M/PROC3) showed higher levels in moderate and severe active disease in CD (1 ± 0.5 vs. 1.8 ± 1.1, p = 0.006). UC patients with moderate to severe activity showed higher levels of type III collagen turnover biomarker (C3M/PROC3) (1.1 ± 0.4 vs. 1.97 ± 1, p = 0.049). C4M correlated positively (r = 0.28, p = 0.03) and PRO-C3 correlated negatively (r = −0.29, p = 0.03) to SES-CD and combined in a multivariate regression model (r = 0.39, p = 0.009). C3M (r = 0.60, p = 0.004) and C4M (r = 0.36, p = 0.039) correlated positively with mMES.

Conclusion

In highly active CD, there is increased type IV collagen degradation and reduced type III collagen formation. Both biomarkers significantly correlate with SES-CD, with increased correlation when combined together. Type III collagen turnover is increased in highly active CD and UC. Biomarkers of types III and IV collagen degradation correlate significantly with mMES. Biomarkers of types III and IV collagen could be used to differentiate highly active CD from UC. Our findings suggest that biomarkers of basement membrane and interstitial matrix remodelling may be used as surrogate markers for monitoring of disease activity for UC and CD.