P084 Response to appendectomy in refractory Ulcerative Colitis appears based on two distinct inflammatory phenotypes

Abstract Background Appendectomy has been suggested to decrease the risk of disease flares in UC, but we recently showed that even therapy refractory patients, appendectomy may improve symptoms a subset patients. Despite several hypotheses, effector mechanism this phenomenon remains unclear. In study characterized gene expression profiles appendices from UC patients either responding or non-responding appendectomy, with aim identify pathways involved response as well guide selection who are optimal candidates for appendectomy. Methods Appendix specimen responders (N=10) and non-responders were included (COSTA-study NCT03912714 off-label appendectomy). Endoscopic was defined steroid-free remission at 12 months without intensified medical treatment. The control group consisted acute appendicitis(N=2). Post-operative biopsies taken appendix coecal base snap frozen. RNA isolated profiling performed using RNAseq. Results Unsupervised clustering indicated two separate clusters, one containing more stromal phenotype expressing ADH1B, IGFBP5, Desmin FLNA other intestinal/B cell (OLMF4, PIGR, CEACAM5 IHGA2). Stainings presence collagen (stromal) versus pancytokeratin (epithelial) confirmed analysis on protein level. Both clusters contained subclusters non-responders. both ‘responder’ subclusters, markers immune activation increased, type differed between ‘stromal responders’ ‘epithelial responders’. increased phase genes present (FABP4, ADIPOQ, SAA1 CXCL8). responders’, activity by mitochondrial activation/oxidative phosphorylation. lacked these markers. We also evaluated differentiating bottom. Indeed, samples largerly clustered according based profile matching appendices. Conclusion Patients distinct patterns, suggesting mechanisms action. Although cases it clearly identified requirement active responses response, identifying groups. This finding consequences further functional studies into future efforts suitable surgery.