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P357 Serological biomarkers of interstitial matrix and basement membrane remodelling correlate to disease activity in Crohn’s disease

L. Godskesen1, M. Lindholm2, J. Høg Mortensen2, A. Krag1, M. Karsdal2, T. Manon-Jensen2, J. Kjeldsen1

1Odense University Hospital, Department of Medical Gastroenterology, Odense, Denmark, 2Nordic Bioscience, Biomarkers and Research, Herlev, Denmark

Background

There is an increased deposition of collagen type III and type IV in the intestinal wall of patients with Crohn’s disease (CD) reflecting an altered remodelling in the interstitial matrix and the basement membrane in the gut. Propeptide of collagen type III (Pro-C3) and MMP-9 degraded collagen type III (C3M) and type IV (C4M) are serological biomarkers reflecting collagen III formation and collagen type III and IV degradation, respectively.

The aim of this study was to evaluate the correlation of Pro-C3, C3M, collagen III turnover ratio (C3M/Pro-C3) and C4M to clinical and endoscopic disease activity in CD.

Methods

63 CD patients were included in a prospective biomarker evaluating study. Seventeen of the 63 CD patients underwent colonoscopy and Simple Endoscopic Score for Crohn’s disease (SES-CD) were recorded. Thirty-five per cent (n = 24) of the patients had active disease defined by Harvey–Bradshaw Index (HBI) > 4. Pro-C3, C3M, and C4M were assessed by competitive enzyme linked immunosorbent assays (ELISAs). Collagen III turnover ratio were calculated and C-reactive protein (CRP) and faecal calprotectin (FC) were measured.

Results

Tables 1 and 2 show the correlations between the biomarkers and the activity scores. C3M was significantly correlated to SES-CD and Collagen III turnover ratio was significantly correlated to HBI and SES-CD. C4M2 was significantly correlated to SES-CD and had a non-significant correlation to HBI. Pro-C3 did not correlate to HBI and SES-CD.

Compared with current biomarkers of disease activity in CD collagen III turnover ratio correlated just as well to HBI as CRP and FC. Collagen III turnover ratio and C3M had a higher correlation to SES-CD than CRP, but FC had the best correlation to SES-CD.

Correlation coefficientp-valueSpearman's rhoPearson's r
Pro-C3−0.350.06−0.30−0.24
C3M0.150.120.230.19
Collagen III turnover ratio0.040.0130.360.31
C4M20.360.0650.280.23
CRP0.790.0130.390.31
FC780.0040.340.37

Correlation between the biomarkers and HBI

Correlation coefficientp-valueSpearman's rhoPearson's r
Pro-C3−0.200.11−0.43−0.41
C3M0.160.020.370.58
Collagen III turnover ratio0.050.0040.460.67
C4M20.47<0.0010.650.81
CRP0.030.880.470.04
FC127<0.0010.710.90

Correlation between the biomarkers and SES-CD.

Conclusion

The data indicate that the collagen III turnover and part of the collagen IV turnover alters with increasing disease activity in CD and that C3M, collagen III turnover ratio and C4M2 might serve as biomarkers of disease activity in CD.