P081 Matrix Metalloproteinase Degraded Biglycan (BGM) and Citrullinated and MMP-degraded Vimentin (VICM) differentiates Crohn's disease from ulcerative colitis.
J.H. Mortensen*1, L. Godskesen2, M.D. Jensen2, L. Klinge2, J. Kjeldsen2, M. Karsdal1, A.-C. Bay-Jensen1, A. Krag2
1Nordic Bioscience, Rheumatology, Herlev, Denmark, 2Odense University Hospital, Gastroenterology , Odense, Denmark
The hallmark of IBD is inflammation, which leads to excessive extracellular matrix remodeling and release of protein fragments into the circulation. Early and accurate diagnosis is essential for optimal treatment. We investigated whether UC or CD contains disease-specific tissue turnover profile, which could be assessed by serological biomarkers
72 CD patients (37 with active disease,>150 CDAI), 56 patients with active UC (St. Marks score>2), and 22 patients with irritable bowel syndrome (IBS) were included. Biomarkers of neutrophil elastase degraded elastin (EL-NE), matrix metalloproteinase (MMP) degraded biglycan (BGM), vimentin (VICM) type 5 collagen (C5M), as well as type % collagen formation (Pro-C5), were evaluated by a competitive ELISA assay system. One way-analysis of variance, Mann-Whitney U-test, and area receiver operator characteristics (ROC) curve analysis were carried out to evaluate the discriminative power of the biomarkers. The biomarkers were adjusted for confounders (age, gender, BMI and smoking). Combination of biomarkers was investigated by a backwards logistic regression model.
Table 1 AUC, sensitivity and specificity of each ROC-analysis
|AUC (CI)||Sensitivity %||Specificity %||Percent of cases correctly classified|
|CD vs. UC: BGM||0.95 (0.92–0.98)||98||80||87 %|
|CD vs. UC: EL-NE||0.85 (0.77–0.91)||76||77||75 %|
|CD vs. UC: Pro-C5/C5M ratio||0.66 (0.57–0.74)||43||85||64 %|
|CD vs. UC: VICM||0.77 (0.72–0.86)||73||86||70 %|
|CD vs. UC: Biomarker combination (BGM, VICM)||0.98 (0.93–0.97)||94||96||94 %|
|CD vs. IBS Biomarker combination (Pro-C5, EL-NE)||0.70 (0.60–0.79)||77||56||77 %|
|UC vs. IBS: BGM||0.97 (0.91–1.0)||98||91||95 %|
|UC vs. IBS: EL-NE||0.93 (0.85–0.97)||86||86||86 %|
|UC vs. IBS: Biomarker combination (BGM, EL-NE)||0.99 (0.94–1.0)||90||100||96 %|
BGM (P<0.0001), EL-NE (P<0.0001), Pro-C5/C5M (P<0.001) were significantly elevated in UC patients compared to CD and IBS patients. VICM was significantly elevated in CD patients compared to UC patients (P<0.0001), and Pro-C5 was significantly elevated in CD patients with active disease compared to UC (P<0.001) and IBS patients (P<0.01). The biomarkers with highest diagnostic accuracy to discriminate CD from UC was BGM (AUC=0.95), EL-NE (AUC=0.85), VICM (AUC=0.76) (table 1) . BGM (AUC=0.97) and EL-NE (AUC=0.93) had the highest diagnostic accuracy to discriminate UC from IBS (table 1). The combination of biomarkers with the highest diagnostic accuracy to differentiate CD from UC was BGM and VICM (AUC=0.98) and Pro-C5 and El-NE to CD from IBS (AUC=0.71)(tabel 1). In addition, Pro-C5 (P<0.05) was significant elevated in CD patients with moderate/severe disease activity compared with low disease activity.
These data provide new insights into the molecular patho-physiological differences of CD and UC. The combined accuracy of the biomarkers, BGM and VICM, demonstrated almost a 100% discriminatory diagnostic power. The role of macrophages (VICM) and MMP-mediated biglycan degradation (BGM) warrants further attention to understand the molecular differences between these related diseases.