Search in the Abstract Database

Abstracts Search 2019

P217 Serological biomarkers of type VI collagen remodelling reflect endoscopically and clinically active Crohn’s disease

M. Lindholm*1,2, L. E. Godskesen2, J. Kjeldsen2, A. Krag2, M. A. Karsdal1, T. Manon-Jensen1, J. H. Mortensen1

1Nordic Biosciene A/S, Biomarkers & Research, Herlev, Denmark, 2University of Southern Denmark and Odense University Hospital, Department of Medical Gastroenterology, Odense, Denmark

Background

The relapsing and transmural inflammation of Crohn’s disease (CD) may cause intestinal tissue damage that eventually may result in surgery. Disease activity in CD patients is assessed by clinical symptoms and macroscopic findings of intestinal inflammation at endoscopy. Type VI collagen reside in the interface of the intestinal interstitial matrix and basement membrane. It affects epithelial cell-fibronectin interaction that is important for cell proliferation, adhesion, and migration. Collagens hold signalling potential, and endotrophin that is released from type VI collagen can stimulate fibroblasts to produce more ECM. Thus, type VI collagen is more than just a structural protein and we investigated if serum biomarkers of its remodelling could serve as surrogate of disease activity in CD patients.

Methods

Serum from 17 CD patients with active (n = 10) and inactive (n = 7) disease based on the simple endoscopic score for CD (SES-CD) were included in this study. Two competitive ELISAs were used to estimate serum levels of degradation and formation of type VI collagen, respectively. One for a neo-epitope of MMP-9-mediated degradation of type VI collagen α3 chain (C6Ma3) and one for endotrophin; C-terminus of released C5 domain of type VI collagen α3 chain (PRO-C6).

Results

Serum C6Ma3 was elevated in CD patients with a SES-CD above 2 compared with patients with a SES-CD of 0–2 (Figure 1A–C). A receiver-operating characteristic (ROC) analysis showed an area under the curve of 1 for C6Ma3 with specificity and sensitivity both at 100% (Figure 1D). The area under the ROC curve for CRP and Fcal were 0.87 and 0.81, respectively (Figure 1E and F). Serum PRO-C6 was lower in CD patients with active disease compared with patients in remission based on the Harvey–Bradshaw Index (HBI) (Figure 1G) and serum PRO-C6 showed an inverse correlation to HBI (Figure 1H).

Conclusion

Our data show that biomarkers of tissue remodelling reflect endoscopically and clinically active CD. MMP mediated destruction of type VI collagen (C6Ma3) was associated with endoscopically active CD and could separate endoscopically active and inactive patients with 100% sensitivity and specificity. Decreased levels of endotrophin (PRO-C6) was associated with clinically active CD and showed an inverse relationship with HBI. This indicates that remodelling of type VI collagen measured by C6Ma3 and PRO-C6 can be used as surrogate markers of endoscopically and clinically active CD, and that fragments and signalling molecules released from type VI collagen are associated with pathological features of CD.

Figure 1. Serum levels of C6Ma3 (A), CRP (B), and Fcal (C) in patients with endoscopically inactive (SES-CD = 0–2) and active (SES-CD >2) CD. Reciever-operating characteristic curves of C6Ma3 (D), CRP (E), Fcal (F), and their ability to distinguish endoscopically active (SES-CD >2) CD from endoscopically inactive (SES-CD = 0–2) CD. Serum levels of PRO-CO (G) in CD patients with inactive (H81 < 5) and active (HBI > 5) CD. Unpaired t-test, area under the ROC curve, and Spearman correlation r were applied. *p ≤ 0.05, **p ≤ 0.01, and ***p ≤ 0.001.

Abstract P217