Background/Purpose: About 10 % of patients with IBD have symptoms that match both Crohn’s disease (CD) and ulcerative colitis (UC), termed inflammatory bowel disease unclassified (IBDU). The hallmark of both diseases is inflammation, which leads to excessive extracellular matrix (ECM) remodeling and release of specific protein fragments, called neoepitopes. However, the pathophysiology, clinical manifestations and treatment is still different among the two diseases. Consequently, to ensure the best possible patient care, accurate diagnosis is essential. Therefore, we speculate that the biomarker profile panel of UC and CD represents a heterogeneous expression pattern, and thus these biomarkers will be a valuable non-invasive diagnostic tool to aid the diagnosis of UC and CD.

Methods: 37 patients with active CD (>150 CDAI) of which 24 had inflammation in colon or colon/ileum, and 56 patients with active UC (St. Marks score >2) were included in this study. All patients had standardized work-up at inclusion, including medical history, physical examination, endoscopy, C-reactive protein. Biomarkers of degraded collagens I, III-IV (C1M, C3M, and C4M), collagen type 1 formation (PINP) and citrullinated and MMP-degraded vimentin (VICM) secreted by activated macrophages  were evaluated by a competitive ELISA assay system. Receiver operator characteristics (ROC) curve analysis was carried out to evaluate the discriminative power of the biomarkers. The combination of biomarkers was investigated by a backward logistic regression model.

Results: The serum level of the biomarkers, C3M and VICM, was significantly different between patients with either active UC or CD. C3M was significantly elevated in patients with UC compared to CD (P=0.039). In contrast, VICM was highly elevated in patients with CD compared to UC (P<0.0001). The biomarkers C3M and VICM showed the highest discriminative value were seen (ROC analysis). The biomarkers were adjusted for demographic variations (age, gender, BMI, and smoking). VICM showed an AUC of 0.76 (P<0.0001) (CD vs. UC), while C3M showed a more modest AUC of 0.62 (P=0.039) (CD vs. UC) (table 1). Furthermore a logistic regression model was developed to find the best combination of the biomarkers. The best combination of biomarkers was VCIM, C3M, and C4M with an AUC of 0.85 (P<0.0001) (table 1). When including only the patients with colon and ileocolonic inflammation the AUC was improved to 0.92 (P<0.0001) (table 1).

Conclusion: These data provide new insights into differences in mechanisms of gut injury in CD and UC. We observed a clinical relevant potential of VICM and C3M as novel biomarkers to differentiate between UC and CD. This suggest that activated macrophages (VICM) and MMP mediated destruction of type III collagen (C3M) are essential disease drivers in IBD, and may discriminate these pathologies.