Abstract Background and aims Inflammatory Bowel Disease is a chronic inflammatory disorder of the gastrointestinal tract, being an emerging and global disease with incidence increasing worldwide and still remaining incurable. We and others have been demonstrating that changes in glycosylation occur during the transition from a normal to pathological condition. Recently it was identified circulating anti-glycan antibodies up to 6 years before the IBD onset, pinpointing glycans as key mediators of pre-clinical inflammation. Our recent data also show that glycosylation alterations can precede disease onset by years, with B cell responses likely playing a critical role in recognizing these changes (Nat Immunol 2024). We hypothesize that host glycosylation is a key molecular driver of chronic inflammation and determinant of the transition from health to disease, modulating both adaptive and humoral immune responses. This project aims to decipher the role of glycan-recognizing B cell and anti-glycan antibodies in triggering and sustaining Crohn’s disease (CD). Methods To test our hypothesis, we will combine multispectral flow cytometry of fresh inflamed intestinal lesions, with spatial multi-omics (CyTOF and Mass Spectrometry Imaging) on FFPE samples, to explore the glycan-B cell axis in CD progression. Moreover, we aim to bring a novel and less invasive biomarker that reflects mucosal glycan-immune interactions by screening serum from CD patients for a multitude of glycan epitopes. Anticipated impact By understanding and characterizing the biology of anti-glycan-specific B cells and their autoantibodies, we hope to demonstrate, for the first time, their pathogenic potential in CD, paving the way for diagnostic tools, not only CD but also other autoimmune diseases that may be associated with a glycan-associated dysfunction and thus loss of self-tolerance.
Alves et al. (Thu,) studied this question.