Fig 1.
Remodelling of the ECM during the inflammatory process in IBD.
The healthy intestinal tissue has intact mucus lining that helps protect the epithelial layer from e.g. bacteria. During the inflammatory state of IBD the mucus layer and the epithelial cell layer is compromised leading to increased bacteria influx. This will, in turn, lead to increased proteinase activity (MMP and NE) and increased infiltration of leukocytes, e.g. macrophages and neutrophil granulocytes. The increased proteinase activity, remodel the ECM that leads to the generation of type V collagen (C5M), biglycan (BGM) and elastin (EL-NE) fragments. Furthermore, local tissue calcium levels also rise as a result of increased cellular turnover. Increased calcium leads to increased citrullination of vimentin that is released from macrophages. Abbreviations: MMP (maxtrix metalloproteinase), NE (neutrolphil elastase), CIT-vimentin (citrullinated vimentin).
Table 1.
Patient demographics.
Fig 2.
Serum levels of the ECM serum biomarkers BGM, EL-NE, Pro-C5, and C5M in CD, UC, IBS and healthy controls.
A) BGM serum level, B) EL-NE serum levels, C) Pro-C5 serum levels, and D) C5M serum level. The error bars represent standard error of the mean (SEM). The asterisks (*) represent P-values, *P<0.05, **P<0.01, ***P<0.001.
Table 2.
Shows the AUC, sensitivity, and specificity, of each ROC-analysis and percentage of cases correctly identified, and combination of biomarkers.
Fig 3.
Serum levels of the biomarkers Pro-C5 and CRP in CD UC patients and correlation of Pro-C5 and CRP in relation to disease activity.
For CD patients the disease activity was assessed by the Crohn’s disease disease acitivity index (CDAI). Remission < CDAI 150, mild = CDAI 150–220, moderate/severe > CDAI 220. Disease activity for UC patients was based on the st. Marks score. Remission < score 3, Mild = score 3–4, Moderate/severe > score 4. A) Pro-C5 serum levels in CD patients, B) CRP levels in CD patients, C) Pro-C5 serum levels in UC patients, D) CRP serum levels in UC patients, E) correlation of Pro-C5 with CDAI as compostite index of the predicted values from the logistic regression model when correcting for CRP levels >5 and use of immunosuppressant drugs, and F) correlation of CRP with CDAI as compostite index of the predicted values from the logistic regression model when correcting for use of immunosuppressant drugs. The error bars represent standard error of the mean (SEM). The asterisks (*) represent P-values, *P<0.05, **P<0.01.
Fig 4.
Serum levels of the ECM serum biomarkers BGM and EL-NE in relation to location in Crohn’s disease and the percentage of colon involvement as a function of the biomarker levels.
The biomarkers were divided into 25% quartiles (Q1, Q2, Q3, Q4), and consisted of 10, 9, 9, and 9 patients respectively. The cumulative sum of the both biomarkers was calculated in divided into quartiles of sum (Q1, Q2, Q3, Q4), and consisted of 5, 9, 13, and 9 patients respectively. A) BGM serum level in patients with colon and ileum involvement, B) EL-NE serum levels with colon and ileum involvement, C) percentage of colon involvement for BGM Q1, Q2, Q3, and Q4, D) percentage of colon involvement for EL-NE Q1, Q2, Q3, and Q4, E) percentage of colon involvement for the sum of quartiles Q1, Q2, Q3, and Q4. The error bars represent standard error of the mean (SEM). Student t-test was applied for figures A and B, the chi-squared test was applied for the figures C, D, and E.
Table 3.
Shows the probability of having colon involvement in Crohn’s disease patients with active disease, by dividing the biomarkers BGM and EL-NE into 25% quartiles and also the sum of quartiles.