S1067 Epithelial Interleukin-8 in Eosinophilic Esophagitis: A Potential New Marker for Disease Activity and Lamina Propria Fibrosis

Introduction: The pathogenesis of eosinophilic esophagitis (EoE) is predominantly driven by T helper 2 cells cytokines such as Interleukin (IL)-4, IL-5, and IL-13, however, IL-8 may play an important role in its inflammation and fibrogenesis. We aim to evaluate IL-8 levels in EoE patients and assess its correlation with histology and fibrosis. Methods: We conducted a longitudinal analysis of EoE patients who underwent endoscopy (January 2021 to May 2025) at EoE center with previously collected esophageal brushing samples available to measure IL-8 levels (sample extracted using cell lysis buffer and the homogenate was centrifuged, then IL-8 was measured using enzyme-linked immunosorbent assay). EoE diagnosis and activity were evaluated per published guidelines, with controls being those with normal endoscopy and histology. Results: We included a total of 87 subjects: 54 confirmed EoE (mean ± standard deviation [SD] age of 10.2 ±5 years; 30 [56%] men), and 33 controls (mean ± SD age of 9.9 ± 5.2 years; 21 (64%) men). Out of 54 EoE patients, 38 were active with no treatment, with significantly higher IL-8 levels (median 814 pg/mL) compared to controls (median 30 pg/mL), P < 0.001. There was a significant reduction of IL-8 levels upon repeat endoscopy in EoE patients with successful treatment (41/54, 76%), P < 0.001. In contrast, EoE patients with failed treatment (13/54, 24%) showed no significant change in IL-8. IL-8 showed a significant positive correlation with peak eosinophilic count (PEC). Receiver operating characteristic analysis for IL-8 to differentiate active EoE patients from controls revealed an optimal IL-8 threshold of 203 pg/mL (85% sensitivity and 100% specificity). Using IL-8 to distinguish active EoE from remission, the optimal threshold is 159 pg/mL, with 91% sensitivity and 78% specificity. IL-8 was significantly elevated in EoE patients with evidence of lamina propria fibrosis (median [interquartile range (IQR)] of 845 [256-1,310] pg/mL), compared to those with no fibrosis (median [IQR] of 207 [57-760] pg/mL), P = 0.002. IL-8 threshold of 784 pg/mL yielded 86% sensitivity and of 58% specificity for predicting fibrosis. Conclusion: Our study demonstrates that epithelial IL-8 is significantly elevated in EoE patients and strongly correlates with PEC, with excellent accuracy in distinguishing active EoE from remission. Additionally, epithelial IL-8 may serve as a predictive marker of lamina propria fibrosis. These findings support the potential role of IL-8 as a new biomarker of disease activity and fibrosis with possible future utility as a therapeutic target.