Lay summary
Inflammatory bowel diseases (IBD) are chronic debilitating intestinal diseases affecting 25,000 people in New Zealand, and costing ~$245 million in healthcare annually. Anti-TNF antibodies are central to IBD therapy; however, most IBD patients lose responsiveness over time. During treatment, IBD patients responsive to anti-TNF antibodies have higher levels of the immunomodulatory cytokines, Type I IFNs (IFN-I), than non-responders. However, a role for IFN-I signaling pathways in driving regeneration associated responses of the intestinal lining (epithelium) in anti-TNF-treated IBD patients is unknown. We propose 1) to validate an innovative IFN-I biomarker panel to predict response to anti-TNFs in a cohort of NZ and US IBD patients; and 2) to elucidate the mechanism(s) driving IFN-I-dependent regenerative responses and epithelial barrier integrity in responsive IBD patients. This study will steer the development of an innovative biomarker panel that will help gastroenterologists tailor therapy for the ~50% of non-responsive IBD patients.