P0050Prognostic value of RIPK3 for progression in Crohn’s disease

Background Receptor-interacting protein kinase-3 (RIPK3) is a key mediator of necroptosis, a regulated form of cell death implicated in the pathogenesis of Crohn’s disease (CD). Increased tissue expression of RIPK3 in inflamed areas of the intestinal mucosa has been found both in experimental models and in patients with active disease, but the prognostic role of the marker remains unclear. This study focuses on the prognostic potential of tissue expression of RIPK3 in patients with Crohn’s disease for the development of severe disease and complications. Methods Tissue expression of RIPK3 was determined immunohistochemically from biopsy samples of 85 patients with Crohn’s disease. Histological activity, clinical activity using the Crohn’s Disease Activity Index (CDAI), disease location and behaviour according to the Montreal classification, and endoscopic activity using the Simple Endoscopic Score for Crohn’s Disease (SES-CD) were also evaluated. The Rutgeerts score was applied in patients who had undergone surgical intervention. Results High expression of the marker was associated with an increased risk of intestinal complications in patients with Crohn’s disease (HR = 3.83; 95% CI 2.34–6.29; p < 0.001), future surgical interventions (HR = 2.16; p = 0.001), comorbidities (HR = 2.35; p = 0.001) and frequent hospitalisations (p = 0.046). The strongest association was observed in cases with intestinal complications. Increased RIPK3 expression was found in patients with frequent relapses (≥2 times per year) compared with those with infrequent relapses (≤1 per year) (181.36 vs 162.50; p = 0.021). A weak positive correlation was observed between relapse frequency and RIPK3 expression (r = 0.250; p = 0.021), indicating that higher relapse rates are associated with increased marker expression. RIPK3 expression was elevated and showed positive correlations with clinical (r = 0.64, p < 0.01), endoscopic (r = 0.59, p < 0.05) and histological (r = 0.68, p < 0.01) activity (Fig. 1). The highest expression was observed in patients with extensive disease involving the upper gastrointestinal tract - L1 + L4 (225.50, p = 0.045) and L2 + L4 (218.00), in those with combined stricturing and penetrating behaviour - B2 + B3 (180.38) and in cases with concomitant perianal disease (181.85; p < 0.05). Conclusion Increased RIPK3 expression in Crohn’s disease is strongly associated with severe clinical, endoscopic and histological activity, intestinal complications, frequent relapses and severe course. Increased RIPK3 expression is an independent predictor of disease progression, further confirming its potential as a novel prognostic marker in Crohn’s disease. Conflict of interest: Dr. Panayotova, Elena: No conflict of interest