Fragments of Citrullinated and MMP-degraded Vimentin and MMP-degraded Type III Collagen Are Novel Serological Biomarkers to Differentiate Crohn’s Disease from Ulcerative Colitis

• Published in: Journal of Crohn's and colitis Vol. 9; no. 10; pp. 863 - 872
• Main Authors: Mortensen, Joachim Høg, Godskesen, Line Elbjerg, Jensen, Michael Dam, Van Haaften, Wouter Tobias, Klinge, Lone Gabriels, Olinga, Peter, Dijkstra, Gerard, Kjeldsen, Jens, Karsdal, Morten Asser, Bay-Jensen, Anne-Christine, Krag, Aleksander
• Format: Journal Article
• Language: English
• Published: UK Oxford University Press 01.10.2015
• Subjects: Adult; Biomarkers - blood; Citrulline; Colitis, Ulcerative - blood; Colitis, Ulcerative - diagnosis; Colitis, Ulcerative - therapy; Collagen Type I - metabolism; Collagen Type III - metabolism; Collagen Type IV - metabolism; Crohn Disease - blood; Crohn Disease - diagnosis; Crohn Disease - therapy; Diagnosis, Differential; Extracellular Matrix - physiology; Female; Humans; Male; Matrix Metalloproteinases; Probiotics - therapeutic use; Proteolysis; Vimentin - metabolism; Inflammatory bowel disease; extracellular matrix remodelling; serological biomarkers
• ISSN: 1873-9946; 1876-4479
• DOI: 10.1093/ecco-jcc/jjv123

Background and Aims: A hallmark of inflammatory bowel disease [IBD] is chronic inflammation, which leads to excessive extracellular matrix [ECM] remodelling and release of specific protein fragments, called neoepitopes. We speculated that the biomarker profile panel for ulcerative colitis [UC] and Crohn’s disease [CD] represent a heterogeneous expression pattern, and may be applied as a tool to aid in the differentiation between UC and CD. Methods: Serum biomarkers of degraded collagens I, III-IV [C1M, C3M, and C4M], collagen type 1 and IV formation [P1NP, P4NP], and citrullinated and MMP-degraded vimentin [VICM] were studied with a competitive ELISA assay system in a cohort including 164 subjects [CD n = 72, UC n = 60, and non-IBD controls n = 32] and a validation cohort of 61 subjects [CD n = 46, and UC n = 15]. Receiver operating characteristic curve analysis and logistic regression modelling were carried out to evaluate the discriminative power of the biomarkers. Results: All biomarkers were corrected for confounding factors. VICM and C3M demonstrated the highest diagnostic power, alone, to differentiate CD from UC with an area under the curve [AUC] of 0.77 and 0.69, respectively. Furthermore, the biomarkers C1M [AUC = 0.81], C3M [AUC = 0.83], VICM [AUC = 0.83], and P1NP [AUC = 0.77] were best to differentiate UC from non-IBD. The best combinations of biomarkers to differentiate CD from UC and UC from non-IBD were VICM, C3M, C4M [AUC = 0.90] and VICM, C3M [AUC = 0.98] respectively. Conclusions: Specific extracellular matrix degradation markers are elevated in IBD and can discriminate CD from UC and UC from non-IBD controls with a high diagnostic accuracy.