Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), is a chronic inflammatory disease of the gastrointestinal tract. In this thesis of Amber Bangma the pathogenesis and means to predict drug responses are studied. In chapter two, we compared the colon of IBD patients to those with both IBD and primary sclerosing cholangitis (PSC), a rare biliary disease associated with IBD, on an mRNA level.
We found activation of different cell types and pathways between the groups. Additionally, we identified DUOX2+ epithelial cells, which are primarily present in the inflamed intestine and may have immunological functions. In chapter three, we studied IBD polygenetic, microbial, environmental and dietary risk scores. We found that patients with IBD have significantly higher genetic and microbial risk scores, and that combining these into a multi-modality risk score could aid early diagnosis.
The second part of this thesis explored how genetic variants may be used to predict responses to IBD medication (i.e. pharmacogenetics). We reviewed literature on well-established pharmacogenetic associations, did not replicate previously identified polygenic risk scores for TNF-alpha antagonist response, and assessed a pharmacogenetic passport that tests for well-established pharmacogenetic associations. We found that testing and adequately treating 24 patients with this passport could prevent one adverse drug reaction. In the final chapter, we analyzed COVID-19-related gene expression in IBD patients, and found significant associations between these genes, inflammation, and IBD medication.
