title: 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.
abstract: OBJECTIVE
  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.
authors.affiliation: Biomarkers and Research, Nordic Bioscience, Herlev, Denmark jhm@nordicbioscience.com.
authors.forename: Joachim Høg
authors.initials: JH
authors.lastname: Mortensen
authors.affiliation: Department of Medical Gastroenterology, Odense University Hospital, Odense, Denmark.
authors.forename: Line Elbjerg
authors.initials: LE
authors.lastname: Godskesen
authors.affiliation: Department of Medical Gastroenterology, Odense University Hospital, Odense, Denmark.
authors.forename: Michael Dam
authors.initials: MD
authors.lastname: Jensen
authors.affiliation: Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands Groningen Research Institute of Pharmacy, Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands.
authors.forename: Wouter Tobias
authors.initials: WT
authors.lastname: Van Haaften
authors.affiliation: Department of Medical Gastroenterology, Odense University Hospital, Odense, Denmark.
authors.forename: Lone Gabriels
authors.initials: LG
authors.lastname: Klinge
authors.affiliation: Groningen Research Institute of Pharmacy, Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: Olinga
authors.affiliation: Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Gerard
authors.initials: G
authors.lastname: Dijkstra
authors.affiliation: Department of Medical Gastroenterology, Odense University Hospital, Odense, Denmark.
authors.forename: Jens
authors.initials: J
authors.lastname: Kjeldsen
authors.affiliation: Biomarkers and Research, Nordic Bioscience, Herlev, Denmark.
authors.forename: Morten Asser
authors.initials: MA
authors.lastname: Karsdal
authors.affiliation: Biomarkers and Research, Nordic Bioscience, Herlev, Denmark.
authors.forename: Anne-Christine
authors.initials: AC
authors.lastname: Bay-Jensen
authors.affiliation: Department of Medical Gastroenterology, Odense University Hospital, Odense, Denmark.
authors.forename: Aleksander
authors.initials: A
authors.lastname: Krag
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D002956:Citrulline; D003093:Colitis, Ulcerative / Q000097:blood* / Q000175:diagnosis* / Q000628:therapy; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism*; D024141:Collagen Type IV / Q000378:metabolism; D003424:Crohn Disease / Q000097:blood* / Q000175:diagnosis* / Q000628:therapy; D003937:Diagnosis, Differential; D005109:Extracellular Matrix / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases; D019936:Probiotics / Q000627:therapeutic use; D059748:Proteolysis; D014746:Vimentin / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D024061:Collagen Type III; D024141:Collagen Type IV; D014746:Vimentin; D002956:Citrulline; D020782:Matrix Metalloproteinases
keywords: Inflammatory bowel disease; extracellular matrix remodelling; serological biomarkers