P0132Prognostic value of RIPK3 for progression in Ulcerative colitis

Background Necroptosis is a regulated form of cell death that has been linked to the initiation and maintenance of the inflammatory process in inflammatory bowel diseases (IBD), including ulcerative colitis (UC). The receptor-interacting protein kinase 3 (RIPK3) is a key mediator in the necroptosis pathway. Increasing evidence suggests that elevated expression of RIPK3 in the intestinal epithelium of UC patients is associated with severe inflammatory activity. The present study aims to determine the prognostic value of RIPK3 in UC patients in relation to disease severity and course. Methods Intestinal biopsies from 85 UC patients were analyzed. RIPK3 expression was evaluated immunohistochemically. Disease activity was assessed according to the Montreal classification (S), total Mayo score (MS), endoscopic Mayo score (MES) and histological analysis. Statistical processing was performed with SPSS v. 20.0, using variance, dispersion, correlation and comparative analyses, as well as risk assessment analysis. Results A positive propotional relationship was observed between RIPK3 expression and disease severity in UC assessed by the Montreal classification (r = 0.354; p = 0.001), total Mayo score (r = 0.481; p < 0.001), endoscopic Mayo score (r = 0.363; p = 0.001) and histological activity (r = 0.735, p < 0.001) (Fig. 1). Overexpression of the marker was associated with severe clinical, endoscopic and histological activity. Risk analysis revealed that high RIPK3 levels were linked to an increased risk of hematochezia (HR = 5.00; 95% CI 1.313–19.046; p < 0.001), higher frequency of diarrheal stools (HR = 1.41; p = 0.002) and infectious complications (HR = 2.85, p = 0.001). It was found that patients with UC and high RIPK3 expression have an increased risk of high disease activity (HR = 21.470; p < 0.001). Conclusion The correlations between RIPK3 expression and the Montreal classification, the total and endoscopic Mayo score, and histological activity, indicate that the marker reliably reflects the severity of the inflammatory process in UC. These data confirm the potential prognostic value of RIPK3 as an independent biomarker for the severity and course of ulcerative colitis. Keywords: RIPK3, necroptosis, ulcerative colitis, IBD, prognostic value Conflict of interest: Dr. Panayotova, Elena: No conflict of interest