Neutrophil Elastase and Elafin in Inflammatory Bowel Diseases: Urinary Biomarkers Reflecting Intestinal Barrier Dysfunction and Proteolytic Activity

Abstract

Background: Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is a chronic inflammatory disorder driven by a complex interplay of immune and proteolytic mechanisms. Neutrophil elastase (NE), released at sites of inflammation, plays a central role by promoting inflammation, degrading the extracellular matrix (ECM), and disturbing intestinal barrier integrity via NF-κB activation and E-cadherin degradation. Elafin, an endogenous NE inhibitor, mitigates proteolytic damage, reinforces the intestinal barrier, and exerts anti-inflammatory effects by suppressing NF-κB and reducing pro-inflammatory cytokines. Since the NE/elafin balance is critical in IBD, assessing their ratio may provide a more precise measure of proteolytic dysregulation. This study aimed to evaluate the diagnostic and prognostic utility of urinary NE, elafin, and their ratio in IBD patients. Methods: Urinary concentrations of NE and elafin were measured by immunoassay in 88 subjects including ulcerative colitis and Crohn's disease patients and healthy individuals. The diagnostic accuracy of these biomarkers was assessed using receiver operating characteristic (ROC) curve analysis. Results: Urinary NE levels were significantly elevated in both UC and CD patients compared to controls, with a 17-fold increase in the UC patients and a 28-fold increase in the CD patients (p < 0.0001). Elafin levels were also increased in IBD patients. The NE/elafin ratio was significantly increased in both disease groups, with a 4.5-fold increase in the UC and 5.6-fold increase in the CD patients compared to healthy controls. The ROC curve analysis demonstrated that the NE/elafin ratio is the most effective biomarker for distinguishing CD patients from healthy individuals (AUC = 0.896), with a high sensitivity (92.9%) and specificity (69.7%), making it a strong diagnostic tool. NE also showed an excellent diagnostic performance both in CD (AUC = 0.842) and UC (AUC = 0.880). The elafin urinary profile had a high diagnostic value, with a better accuracy in the UC patients (AUC = 0.772) than the CD patients (AUC = 0.674), though it was inferior to NE and NE/elafin. Conclusions: Our findings indicate that urinary NE, elafin, the and NE/elafin ratio have significant diagnostic value in differentiating IBD patients from healthy controls. The NE/elafin ratio and NE proved to be the most reliable urinary biomarkers in both CD and UC diagnosis, with a high predictive value and strong discriminatory power.

Keywords: Crohn’s disease; biomarker; elafin; extracellular matrix; inflammatory bowel disease; neutrophil elastase; proteolytic balance; ulcerative colitis.

Figure 1

Urinary excretion of elafin and NE and the NE/elafin ratio in patients with ulcerative colitis, and Crohn’s disease and healthy individuals; (A), urinary profile of neutrophil elastase in analyzed groups; (B), urinary profile of elafin in analyzed groups; (C), Neutrophil elastase/elafin ratio in analyzed groups. Data with statistical significance has been marked as * p < 0.0005; ** p < 0.0001.

Figure 2

ROC curve of NE, elafin, and NE/elafin ratio as diagnostic biomarkers of UC and CD; (A), ROC curve of analyzed parameters as diagnostic biomarkers of UC group; (B), ROC curve of analyzed parameters as diagnostic biomarkers of UC group.