Inge Jacobs, Matthias Ceulemans, Matthias Lenfant, Jonathan Cremer, Gert De Hertogh, Marc Ferrante, João Sabino, Séverine Vermeire, Christine Breynaert, Tim Vanuytsel, Bram Verstockt
We confirmed enrichment of total eosinophils in inflamed colonic tissue, characterized by an increase in B-Eos and a reduction in A-Eos, resulting in a decreased A-Eos/B-Eos ratio. Exploratory analyses suggest that vedolizumab is associated with reduced B-Eos, increased A-Eos, and restoration of the A-Eos/B-Eos ratio, raising the hypothesis that this therapy may differentially modulate mucosal eosinophil biology. These findings identify distinct eosinophil subsets as potential biomarkers and therapeutic targets in UC and provide a biological framework for future mechanistic studies.
BACKGROUND AND AIMS: Despite the importance of eosinophils in histologic scoring systems of ulcerative colitis (UC), the impact of advanced therapies on eosinophils is poorly understood. Additionally, data regarding distinct eosinophil subsets in UC are scarce.
METHODS: Colonic immune cells from 20 patients were analyzed by flow cytometry, alongside matched stool samples measuring fecal calprotectin and eosinophil-derived neurotoxin. In a separate cohort of 29 UC patients starting advanced therapy, immune cells from blood and colon were profiled at baseline and post-induction. Treatment response was defined as a Mayo endoscopic subscore of 0-1. A retrospective cohort (n = 21) was used to validate our findings.
RESULTS: Inflamed colonic tissue was characterized by an increased abundance of total eosinophils (P = .007), with an enrichment of B-Eos (CD80- PD-L1-) and depletion of A-Eos (CD80+ PD-L1+ active eosinophils) (both P < .0001) compared with unaffected tissue (correlated with histological activity RHI, P = .003). Endoscopic response to advanced therapy was associated with a reduction in total eosinophils (P = .0008) and various other immune cells, whereas nonresponse showed significant immune remodeling. Exploratory analyses in patients treated with vedolizumab (n = 11) demonstrated reductions in colonic total eosinophils (P = .07) and B-Eos (P = .008), together with an increase in A-Eos (P = .0003), resulting in an increased A-Eos/B-Eos ratio irrespective of endoscopic outcome.
CONCLUSION: We confirmed enrichment of total eosinophils in inflamed colonic tissue, characterized by an increase in B-Eos and a reduction in A-Eos, resulting in a decreased A-Eos/B-Eos ratio. Exploratory analyses suggest that vedolizumab is associated with reduced B-Eos, increased A-Eos, and restoration of the A-Eos/B-Eos ratio, raising the hypothesis that this therapy may differentially modulate mucosal eosinophil biology. These findings identify distinct eosinophil subsets as potential biomarkers and therapeutic targets in UC and provide a biological framework for future mechanistic studies.