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P301 A serological biomarker of type VIII collagen that contains the anti-angiogenic signalling molecule, vastatin, is associated with the extension of disease in ulcerative colitis

M. Lindholm*1,2, L. E. Godskesen2, L. L. Langholm1, J. Kjeldsen2, A. Krag2, M. A. Karsdal1, T. Manon-Jensen1, J. H. Mortensen1

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

Background

Ulcerative colitis (UC) is characterised by superficial inflammation that starts in the rectum and can extend proximally to affect the entire colon. Endoscopy is used to diagnose patients in terms of extension of disease; however, this is invasive and cannot always be completed, for example, if the colon is too severely inflamed. The epithelial and endothelial basement membrane (BM) is an abundant extracellular matrix (ECM) of the intestine. Type VIII collagen is directly associated with the BM and the C-terminus of this collagen contains the anti-angiogenic signalling molecule, vastatin. Due to the abundant vasculature in the intestine, we investigated if a serum biomarker that targets the vastatin site of type VIII collagen was associated with the degree of inflammation in UC.

Methods

Serum was collected from 61 UC Patients who were endoscopically recorded for extension of disease: remission, proctitis, left-sided, pancolitis, and unknown. Endoscopy could not be completed in patients with unknown extension of disease; however, five out of six unknown patients had at least left-sided colitis, but most possibly pancolitis. Rat serum from acute (n = 10) and chronic dextran sulphate sodium (DSS) colitis (n = 39) were included. A competitive ELISA for the C-terminus of type VIII collagen (PRO-C8) was used to estimate serum levels of type VIII collagen/vastatin.

Results

PRO-C8 serum levels were elevated in UC patients with proctitis (p = 0.003), left-sided (p = 0.008), pancolitis (p = 0.002), and unknown (p = 0.0003) extension of disease compared with patients in endoscopical remission. In addition, PRO-C8 serum levels were elevated in unknown (p = 0.036) and pancolitis (p = 0.03) patients compared with proctitis. The levels were also elevated in unknowns (p = 0.04) compared with left-sided, for which pancolitis patients had a tendency (p = 0.065) of higher PRO-C8 levels (Figure 1A). Serum PRO-C8 was confirmed to be increased in both acute and chronic DSS colitis (Figure 1B and C).

Conclusion

PRO-C8, containing the anti-angiogenic signalling molecule vastatin, was associated with extension of disease in UC patients and was elevated in patients for which endoscopy could not be completed. Increased PRO-C8 was shown to originate from intestinal inflammation in DSS colitis in rats. Thus, PRO-C8 may be a serological biomarker that reflects intestinal tissue inflammation based on extension of disease. This also indicates that UC patients with broad tissue involvement may have an altered collagen signalling and that ECM signals are part of the disease pathology.

Abstract P301 – Figure 1. Serum levels of PRO-C8 in UC patients grouped by extension of disease (A). Endoscopy was not completed for patients with unknown extension of disease. Five out of six unknowns have at least left-sided colitis, and possibly pancolitis. Serum levels of PRO-C8 in rats with acute (B) and chronic (D) DSS colitis. Unpaired t test and Mann–Whitney test were applied. *p < 0.05, **p < 0.01, ***p < 0.001.