P308 CPa9-HNE: A NEUTROPHIL-DERIVED FRAGMENT OF CALPROTECTIN MEASURED IN SERUM CAN MONITOR ENDOSCOPIC AND CLINICAL DISEASE ACTIVITY IN ULCERATIVE COLITIS

Abstract

Abstract Background Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) presenting in remitting ulcerations of the colonic mucosa and submucosa. Mucosal healing is therefore an important treatment target. While fecal calprotectin is a common biomarker used to monitor mucosal healing in UC, patient compliance is low due to a preference for serological markers. This study aimed at investigating the association of serum calprotectin [CPa9-HNE], a non-invasive neo-epitope biomarker of neutrophil activity, with both clinical and endoscopic disease activity in UC. Methods The cohort included 49 patients with active UC and 50 and healthy controls (HC). Endoscopic and clinical disease activity was assessed using the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and the full Mayo score. Serum calprotectin [CPa9-HNE] was measured, reflecting a human neutrophil elastase-derived fragment of calprotectin. Spearman’s rank correlation was applied. Group differences were evaluated using Kruskal-Wallis with Dunn‘s test, bonferroni corrected for MCP. Diagnostic and discriminative capabilities were assessed using receiver operating characteristic (ROC) statistics with are under the curve (AUC). Results CPa9-HNE was significantly elevated in patients with UC compared to HC (ng/ml [IQR]: 32.4 [29.0–52.3] vs. 26.0 [22.6–29.0], p<0.0001) and presented acceptable discriminative capabilities (AUC [95% CI]: 0.77 [0.67–0.87], p<0.0001). CPa9-HNE showed a moderate positive correlation to UCEIS and Mayo (ρ=0.42; ρ=0.48, both p<0.01). When patients were stratified according to endoscopic disease activity (UCEIS), CPa9-HNE was significantly elevated in patients with severe disease compared to those with mild disease (ng/ml [IQR]: 55.6 [40.9–66.4] vs. 28.9 [24.6–31.1], p<0.01) and could accurately discriminate between the two groups (fig 1A-B). Similarly, when patients were grouped according to the full Mayo score, CPa9-HNE was significantly elevated in patients with mild vs. severe disease (29.1 [24.3–32.4] vs. 62.9 [55.2–67.5], p<0.01) and moderate vs. severe disease (32.0 [29.2–39.2] vs. 62.9 [55.2–67.5], p<0.01), and could accurately discriminate between the groups (fig 1C-E). Conclusion CPa9-HNE was elevated in patients with UC compared with healthy subjects. Furthermore, CPa9-HNE accurately discriminated between patients with mild and severe endoscopic disease based on the UCEIS score, as well as between patients with mild, moderate, and severe clinical disease activity according to the full Mayo score. These findings highlight the potential use of CPa9-HNE as a non-invasive tool to monitor both endoscopic and clinical disease activity in UC, with the potential of guiding treatment decisions and better aligning with patient preferences.