Clinical and Experimental Gastroenterology (Feb 2022)
Mucosal Gene Transcript Signatures in Treatment Naïve Inflammatory Bowel Disease: A Comparative Analysis of Disease to Symptomatic and Healthy Controls in the European IBD-Character Cohort
Abstract
Simen Svendsen Vatn,1,2,* Jonas Christoffer Lindstrøm,3,4,* Aina EF Moen,1,4,5 Stephan Brackmann,1,2 Tone M Tannæs,1,5 Christine Olbjørn,1,6 Daniel Bergemalm,7 Åsa V Keita,8 Fernando Gomollon,9 Trond Espen Detlie,1,2 Torben Lüders,5 Rahul Kalla,10 Alex Adams,10,11 Jack Satsangi,10,11 Jørgen Jahnsen,1,2 Morten H Vatn,1 Jonas Halfvarson,7 Petr Ricanek,2 Hilde Nilsen1,5 On behalf of IBD-CHARACTER consortium1Department of Clinical Molecular Biology, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; 2Department of Gastroenterology, Division of Medicine, Akershus University Hospital, Lørenskog, Norway; 3Health Services Research Unit (HØKH), Akershus University Hospital, Lørenskog, Norway; 4Department of Methods Development and Analytics, Division of Infectious Disease Control and Environmental Health, Norwegian Institute of Public Health, Oslo, Norway; 5Section for Clinical Molecular Biology (EpiGen), Akershus University Hospital, Lørenskog, Norway; 6Department of Pediatric and Adolescent Medicine, Akershus University Hospital, Lørenskog, Norway; 7Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; 8Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden; 9Digestive Diseases Unit, IIS Aragón, Zaragoza, Spain; 10Gastrointestinal Unit, Centre for Genomics and Molecular Medicine, Division of Medical and Radiological Sciences, University of Edinburgh, Edinburgh, UK; 11Translational Gastroenterology Unit, Medical Sciences/ Experimental medicine Division, University of Oxford, Oxford, UK*These authors contributed equally to this workCorrespondence: Simen Svendsen Vatn, Akershus University Hospital, Postbox 1000, Lørenskog, 1478, Norway, Tel +47 94277594, Email [email protected]: Studies of the mucosal transcriptomic landscape have given new insight into the pathogenesis of inflammatory bowel disease (IBD). Recently, the predictive biomarker potential of gene expression signatures has been explored. To further investigate the mucosal gene expression in IBD, we recruited a cohort of treatment naïve patients and compared them to both symptomatic and healthy controls.Methods: Altogether, 323 subjects were included: Crohn’s disease (N = 75), ulcerative colitis (N = 87) and IBD unclassified (N = 3). Additionally, there were two control groups: symptomatic controls (N = 131) and healthy controls (N = 27). Mucosal biopsies were collected during ileocolonoscopy and gene expression in inflamed and non-inflamed mucosa was explored. Gene expression profiling was performed using Agilent G3 Human Gene Expression 860K v3 One-Color microarray. We recorded information about treatment escalation to anti-TNF agents or surgery, and anti-TNF response, to explore predictive opportunities of the mucosal transcriptome.Results: Gene expression profiles in symptomatic controls in whom IBD had been excluded resembled that of IBD patients and diverged from that of healthy controls. In non-inflamed Crohn’s disease and ulcerative colitis, gene set enrichment analysis revealed dysregulation of pathways involved in basic cellular biological processes. Mitochondria-associated pathways were dysregulated both in non-inflamed and inflamed Crohn’s disease and ulcerative colitis (> 2.6 normalized enrichment scores
