A Fragment of Collagen Type VI alpha-3 chain is Elevated in Serum from Patients with Gastrointestinal Disorders

Signe Holm Nielsen, Joachim Høg Mortensen, Nicholas Willumsen, Daniel Guldager Kring Rasmussen, Ditte J. Mogensen, Antonio Di Sabatino, Giuseppe Mazza, Lars Nannestad Jørgensen, Paolo Giuffrida, Massimo Pinzani, Lone Klinge, Jens Kjeldsen, Diana Julie Leeming, Morten Asser Karsdal, Federica Genovese

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Abstrakt

Extracellular matrix (ECM) remodeling is a hallmark of the pathology of gastrointestinal disorders. Collagen type VI (COL6) is produced by fibroblasts, and the COL6 α3-chain has shown to be elevated in patients with ulcerative colitis (UC), Crohn's disease (CD) and colorectal cancer (CRC). Measuring COL6α3 in serum may therefore have potential as a biomarker for gastrointestinal disorders. The aims of this study were to develop and validate a competitive ELISA targeting a specific neo-epitope of COL6α3 and evaluate its associations with the gastrointestinal disorders UC, CD and CRC, in comparison to healthy controls. A monoclonal antibody was raised against a matrix metalloproteinase-2 and -9 specific cleavage site of COL6α3 (C6Mα3) and employed in a competitive enzyme-linked immunosorbent assay (ELISA). The assay was developed and technically validated. Levels of C6Mα3 were measured in serum from patients with UC (n = 58), CD (n = 44) and CRC (n = 39) and compared to healthy controls (n = 32). The levels of C6Mα3 were elevated in patients with UC, CD and CRC patients compared to healthy controls (all p < 0.0001). The area under the receiver operating characteristics (AUROC) curve for separation of patients with UC from healthy controls was 0.972 (95% CI: 0.925-1.020, p < 0.0001), with CD from healthy controls was 0.947 (95% CI: 0.885-1.009, p < 0.0001) and with CRC from healthy controls was 0.890 (95% CI: 0.809-0.972, p < 0.0001). We developed a technically robust assay targeting a fragment of COL6, which was elevated in serum from patients with UC, CD and CRC.

OriginalsprogEngelsk
Artikelnummer5910
TidsskriftScientific Reports
Vol/bind10
Antal sider8
ISSN2045-2322
DOI
StatusUdgivet - 3. apr. 2020

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  • Citationsformater

    Holm Nielsen, S., Mortensen, J. H., Willumsen, N., Rasmussen, D. G. K., Mogensen, D. J., Di Sabatino, A., Mazza, G., Jørgensen, L. N., Giuffrida, P., Pinzani, M., Klinge, L., Kjeldsen, J., Leeming, D. J., Karsdal, M. A., & Genovese, F. (2020). A Fragment of Collagen Type VI alpha-3 chain is Elevated in Serum from Patients with Gastrointestinal Disorders. Scientific Reports, 10, [5910]. https://doi.org/10.1038/s41598-020-62474-1