Immunogenetic Profiling of Colonic Mucosa in Ulcerative Proctitis to Identify Disease Progression Signatures

Background and aims Ulcerative proctitis (UP) appears to behave differently from extended colitis, but differences between these two disease manifestations are poorly understood and progression of UP disease progression is unpredictable. This research project aims to investigate the mucosal immune profiles of patients with ulcerative proctitis (UP), to better understand this disease and identify patients with and without disease progression. Methods We will employ multiplex immunoprofiling, particularly mass cytometry (CyTOF), to characterize the immune profiles of mucosal biopsies from UP patients. Biopsies collected from patients with and without disease progression, defined as endoscopic extension from proctitis (Montreal E1) to left-sided (E2) or pancolitis (E3) will be analysed. Panels targeting epithelial and immune cell subsets associated with UC pathogenesis will be employed, and high-dimensional analyses will be performed to compare immune signatures between UP patients with disease progression versus those without. Anticipated impact This research project will provide in-depth immunogenetic profiling of UP patients with and without disease progression, enhancing our ability to predict those at risk for disease progression. Patients at low risk for disease progression may potentially be referred back to primary care, while those at higher risk may require closer monitoring. Additionally, knowledge on the immunogenetic profiles of UP patients may allow patient stratification and aid the development of targeted therapies with the appropriate mechanism of action, ultimately improving patient outcomes.