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Investigating Intestinal Inflammation in DSS-induced Model of IBD
Published on: February 1, 2012
Fecal Dipeptidyl Peptidase-4: An Emergent Biomarker in Inflammatory Bowel Disease
Pedro Pinto-Lopes1,2,3, Francisco Melo3, Joana Afonso3,4
1Department of Internal Medicine, Faculty of Medicine, Centro Hospitalar Universitário São João, Porto, Portugal.
Introduction:
Dipeptidyl peptidase-4 (DPP-4) is a membrane-bound glycoprotein that acts as a receptor but also exists in a soluble form. It has been recognized as a mediator of inflammation and considered a biomarker in inflammatory bowel disease (IBD).
Methods:
We evaluated a prospectively recruited cohort, consisting of 101 patients with IBD, using validated clinical indexes; 22 patients with ulcerative colitis (UC) underwent endoscopic evaluation. Fecal DPP-4 (fDPP-4) levels were analyzed and correlated with clinical scores, Mayo endoscopic score (in UC patients), serum DPP-4, C-reactive protein, and fecal calprotectin. Immunohistochemical staining for DPP-4 in intestinal biopsies was also performed.
Results:
When compared with remitters, median fDPP-4 levels were higher in patients with ileal Crohn's disease (CD) (7,584 [1,464-7,816] vs 2,104 [630-2,676] ng/mL, P = 0.015) and lower in patients with UC exhibiting clinical activity (1,213 [559-1,682] vs 7,814 [2,555-7,985] ng/mL, P < 0.001). Patients with UC presenting endoscopic activity also had lower levels than remitters (939 [559-1,420] vs 7,544 [4,531-7,940] ng/mL, P = 0.006). Fecal DPP-4 discriminated clinical activity from remission with areas under the curve of 0.76 (95% confidence interval [CI] 0.58-0.94, P = 0.015) and 0.80 (95% CI 0.68-0.93, P < 0.001) in CD and UC, respectively; it allowed to differentiate endoscopic activity in patients with UC, with areas under the curve of 0.84 (95% CI 0.63-1.00, P = 0.009). Immunohistochemical analysis revealed higher DPP-4 apical expression in UC remitters, but no statistically significant differences were revealed between patients with ileal CD.
Discussion:
Our results suggest that fDPP-4 can be used as a biomarker of IBD activity, particularly in UC. The expression profiles in intestinal tissue might represent a functional compartmentalization of DPP-4 expression.
Insights
Fecal dipeptidyl peptidase-4 (DPP-4) levels can indicate inflammatory bowel disease (IBD) activity. Higher fecal DPP-4 suggests Crohn
Area of Science:
- Gastroenterology and Immunology
- Biomarker Discovery
- Inflammatory Bowel Disease (IBD) Research
Background:
- Dipeptidyl peptidase-4 (DPP-4) is a glycoprotein involved in inflammation and recognized as a potential biomarker in inflammatory bowel disease (IBD).
- Understanding DPP-4's role in IBD pathogenesis and its utility as a diagnostic marker is crucial for patient management.
Purpose of the Study:
- To evaluate fecal DPP-4 (fDPP-4) as a biomarker for assessing disease activity in patients with IBD.
- To correlate fDPP-4 levels with clinical and endoscopic disease severity in Crohn's disease (CD) and ulcerative colitis (UC).
Main Methods:
- A cohort of 101 IBD patients was prospectively studied, including clinical assessments and endoscopic evaluations for 22 UC patients.
- Fecal DPP-4 levels were measured and correlated with clinical indices, endoscopic scores, serum DPP-4, C-reactive protein, and fecal calprotectin.
- Immunohistochemical staining for DPP-4 was performed on intestinal biopsies.
Main Results:
- Higher median fDPP-4 levels were observed in ileal CD patients compared to remitters (P = 0.015).
- Lower fDPP-4 levels were found in UC patients with clinical (P < 0.001) and endoscopic activity (P = 0.006) compared to UC remitters.
- fDPP-4 demonstrated good discriminatory ability for clinical and endoscopic activity in CD and UC, with areas under the curve ranging from 0.76 to 0.84.
Conclusions:
- Fecal DPP-4 serves as a valuable biomarker for IBD activity, particularly in ulcerative colitis.
- The differential expression profiles of DPP-4 in intestinal tissue may indicate functional compartmentalization within the gut.
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