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P235 Serological biomarkers of interstitial matrix and basement membrane remodelling correlate the Modified Mayo Endoscopic Score (mMES) for ulcerative colitis

J. Mortensen1, L.E. Godskesen2, M. Lindholm1, A. Krag2, M.A. Karsdal1, T. Manon-Jensen1, J. Kjeldsen2

1Nordic Bioscience A/S, Biomarkers and Research, Herlev, Denmark, 2Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark

Background

Endoscopy is a mainstay in ulcerative colitis (UC) for disease activity monitoring. The modified Mayo Endoscopic Score (mMES) for UC takes into account disease extent and hereby additional objectivity can be achieved for endoscopic assessment. However, endoscopic evaluation of the intestinal mucosa is time-consuming and inconvenient for the patients. Therefore, surrogate biomarkers for endoscopic examinations are warranted. The aim of this study was to evaluate serological neo-epitope biomarkers of type IV collagen degradation (C4M) and formation (PRO-C4), type III collagen degradation (C3M), type V collagen formation (PRO-C5) and macrophage activity (VICM) and their association with the mMES for UC.

Methods

Endoscopic disease activity was scored using mMES for UC patients (n = 63). Patients were stratified according to the disease activity severity based on mMES (remission = 0–1, mild = 2–4, moderate = 5–6, severe >6). ELISA was applied for biomarker measurements (C4M, PRO-C4, C3M, PRO-C5 and VICM) in serum. Pearson correlations and one-way-ANOVA with FDR correction were applied for statistical analysis. A multivariate regression model was developed in order to combine the ECM biomarkers as a composite index. This model was correlated with the mMES and compared with FC and C-reactive protein (CRP) levels.

Results

All the biomarkers correlated to mMES (VICM: r = 0.35, p = 0.0063; PRO-C5: r = 0.33, p = 0.009; C3M: r = 0.32, p = 0.011; C4M: r = 0.28, p = 0.0255; PRO-C4: r = 0.25, p = 0.044). Stratification of the patients revealed that VICM, C3M, and C4M serum levels were significantly elevated in UC patients with severe mMES compared with patients in remission (VICM: p = 0.0158, C3M: p = 0.04), mild disease activity (VICM: p = 0.0002, C3M: p = 0.0049, C4M: p = 0.0084) and moderate disease activity (VICM: p = 0.0166). Biomarkers that correlated significantly with the mMES were included in the multivariate regression model as a composite biomarker index. The biomarker model correlated significantly with mMES (r = 0.45, p = 0.0002) (Figure 1A) and the model was also able to discriminate between the different stages of disease activity (p = 0.0007) (Figure 1D). FC correlated with mMES (r = 0.48, p = 0.0001) (Figure 1B and E), however CRP did not correlate with mMES (Figure 1C and F).

Conclusion

The combined tissue-remodelling biomarkers correlated significantly with mMES for UC. The ECM serological biomarkers performed better than CRP, and equally good as FC. Thus, serological biomarkers of ECM remodelling, especially basement membrane degradation, interstitial matrix degradation and macrophage activity biomarkers may be used as surrogate markers for endoscopic disease activity assessment for UC.