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

J Crohns Colitis. 2015 Oct;9(10):863-72. doi: 10.1093/ecco-jcc/jjv123. Epub 2015 Jul 17.


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.

Keywords: Inflammatory bowel disease; extracellular matrix remodelling; serological biomarkers.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*


  • Biomarkers
  • Collagen Type I
  • Collagen Type III
  • Collagen Type IV
  • Vimentin
  • Citrulline
  • Matrix Metalloproteinases