P0455 An eosinophilic endotype of ulcerative colitis is linked with a more complicated disease phenotype
Authors: Jantsch A , Vorhaben T , Yalcin F , Hinrichsen F , Lebich J , Bourgery M , Welz L , Labrenz J , Lüschen S , Röcken C , Aden K , Rosenstiel P , Schreiber S , Tran F 
Published: January 2025

Abstract

Background
The course, extent, and therapeutic response in ulcerative colitis (UC) are highly heterogeneous. The spatial and immunological variability of chronic inflammation in UC may explain the inconsistent responses to advanced therapies. Eosinophils are found in both inflamed and non-inflamed tissue at varying numbers, though their exact role in UC pathophysiology and clinical significance is still unclear, despite being part of the Geboes score criteria. We therefore aimed to systematically assess the clinical characteristics of UC patients with tissue eosinophilia as reported by pathology, hypothesizing that this group represents a molecularly distinct sub-entity of UC.

Methods
We screened all pathology reports from endoscopies performed on IBD patients at the University Hospital Schleswig-Holstein (UKSH, Kiel), between 2010 and 2022. Of 10,552 reports, we identified 179 cases with confirmed UC diagnosis, informed consent, and sufficient clinical and follow-up data. Clinical data extracted from electronic medical records included baseline demographics, histo-endoscopic disease activity, routine blood markers, and 24-month follow-up for UC-related hospitalization, surgery, and therapy escalation (with advanced therapies or systemic steroids). A molecular cross-sectional UC cohort (n=587) recruited at UKSH during the same period served as the control group. Early disease was defined as a disease duration of less than 24 months with no prior advanced therapies.

Results
Patients with tissue eosinophilia were younger (median age: 36 vs. 42 years, p=0.0095), had a lower BMI (25.20 vs. 33.90 kg/m², p&lt;0.0001), higher blood eosinophil counts (0.20 vs. 0.09 /nL, p=0.0003), elevated CRP levels (3.88 vs. 2.47 mg/L, p=0.0342), and higher Endoscopic Mayo Scores (2 vs. 1, p=0.0003) compared to controls. However, the Nancy Histology Index (2 vs. 2, p&gt;0.05) as well as the sex ratio (male sex: 56.42% vs. 57.99%; p&gt;0.05) was similar between the groups. Within 24 months of follow-up, the tissue eosinophilia group had a higher likelihood of disease-related hospitalization (Log-rank test: p=0.0029) and UC-related surgery (p=0.0223). When stratified by disease phase, these findings were significant only in patients in the late disease phase (hospitalization: p=0.0345; surgery: p=0.0012).

Conclusion
Tissue eosinophilia in patients in the later stage of their disease is associated with worse long-term outcomes, such as UC-related hospitalization and surgery within 2 years. These findings hint towards the existence of a type-2 immunity-associated endotype of UC. Further studies on eosinophil count and their activation states are needed to define functional signatures of this novel group of patients that might benefit from therapies targeting type-2-cytokines.

References
This project has received funding from the DFG Cluster of Excellence 2167 “Precision medicine in chronic inflammation”, the BMBF (e:Med Network iTREAT 01ZX2202A), EKFS (2022_EKMS.23), the PATHWAYS Global Innovation Grant program (Sanofi & Regeneron), and the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 831434 (3TR) and No 853995 (ImmUniverse).The JU receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. The content provided in this publication reflects the author’s views only. Neither the Innovative Medicines Initiative (IMI JU) nor the European Commission are responsible for any use that may be made of the information it contains.