P83 Understanding Differences in Serum and Mucosal Immunopathotypes in Crohn’s Disease

Baer, H. M. et al. (2021) P83 Understanding Differences in Serum and Mucosal Immunopathotypes in Crohn’s Disease. BSG Campus, 21-29 Jan 2021. (doi: 10.1136/gutjnl-2020-bsgcampus.158)

Abstract

Introduction: Crohn’s disease (CD) is a chronic inflammatory condition of the gastrointestinal tract, characterised by an aberrant immune response towards commensal microbiota. Despite the availability of target-specific front-line therapeutics, 30–40% of CD patients still require surgery to manage disease. This project aims to identify different systemic and mucosal CD immunopathotypes and map their associations to distinct treatment responses and behaviours. Methods: To study local immune response in CD, colonic mucosal biopsies of inflamed patients (CD, n=4) and non-IBD controls (NC, n=6) were analysed by bulk RNA sequencing. Raw counts were normalised using DESeq and further analysed in R studio with a specific pipeline to select differentially expressed genes associated with the immune system. All findings were validated in a selection of three cohorts comparing gene expression of colonic inflamed CD tissue with non-IBD controls (nCD=36, nNC=24). Differences in the systemic immune response were studied in two separate cohorts by isolating plasma and peripheral mononuclear cells (PBMCs) from fresh whole blood of CD patients with different levels of disease activity (n=30) and NCs (n=42). Subsequently, cytokine levels and leukocyte frequencies were measured using multiplex assays and flow cytometry analysis. Results: Gene expression analysis of colonic mucosal tissue biopsies highlighted an immunophenotype driven by macrophage and neutrophil activation and infiltration. After validating this gene cluster in a selection of cohorts, we find that CD patients with colonic active disease can be stratified into three different groups based on their macrophage activation phenotype. In the peripheral blood, we observed that patients have different levels of systemic disease activation, characterised by their leukocyte and cytokine concentrations, independent of their disease activity. Conclusions: Our analyses of mucosal tissue and peripheral blood have provided evidence of different immunopathotypes, both mucosal and systemic. Ongoing work will involve the correlation of these phenotypes with clinical information, such as treatment response and disease progression, to better understand whether pathotypes predict disease behaviour in CD.

• Item Type: Conference or Workshop Item
• Additional Information: Conference abstract published in Gut, Vol.70(suppl1):A83.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Cole, Mr John and Milling, Professor Simon
• Authors: Baer, H. M., McDonald, E., Ferguson, A. N., Scott, A.-M., Khan, M. I., Bain, K. A., Ijaz, U. Z., Cole, J. J., Ramanujam, M., Nibbs, R. J. B., Gaya, D. R., and Milling, S. W. F.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Research Centre: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology
• ISSN: 0017-5749