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Updated: Jun 18, 2025
Author Spotlight: Investigating the Pathophysiology of Eosinophilic Esophagitis
Published on: May 10, 2024
TH2 cell compensatory effect following benralizumab treatment for eosinophilic gastritis
Netali Ben-Baruch Morgenstern1, Yrina Rochman1, Julie M Caldwell1
1Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Background:
Eosinophil accumulation is a main feature of eosinophilic gastritis (EoG) and is associated with its histologic diagnosis and pathology. However, a recent clinical trial has demonstrated that EoG endoscopic, noneosinophil histologic, and clinical features remain persistent despite complete eosinophil depletion.
Objective:
Our aim was to examine gastric T-cell composition and associated cytokine levels of patients with EoG following benralizumab-induced eosinophil depletion versus following administration of placebo.
Methods:
A cohort of subjects with EoG from a subset of subjects who participated in a recent phase 2 benralizumab trial was treated for 12 weeks with administration of 3 doses of benralizumab (anti-IL-5 receptor α antibody [n = 5]) or placebo (n = 4). Single-cell suspensions obtained by gastric biopsy were stimulated with phorbol 12,13-dibutyrate and ionomycin in the presence of brefeldin A and monensin. Harvested cells were fixed, stained, and analyzed by flow cytometry to examine T-cell populations and associated cytokines.
Results:
Following benralizumab treatment but not placebo, blood and gastric eosinophil levels decreased 16-fold and 10-fold, respectively. Whereas histologic score and features were significantly decreased, no change was observed in endoscopic score and features. Following complete eosinophil depletion with benralizumab, gastric TH2 cell levels were 3-fold higher than the levels in the patients with EoG who were given placebo; and the levels of associated type 2 cytokine production of IL-4, IL-5, and IL-13 in the benralizumab-treated patients were, respectively, 4-, 5.5-, and 2.5-fold, higher than those in the placebo-treated patients.
Conclusion:
We have identified a putative positive feedback loop whereby eosinophil depletion results in a paradoxic increase in levels of TH2 cells and derived cytokines; this finding suggests an explanation for the limited success of eosinophil depletion as monotherapy in eosinophil-associated gastrointestinal disorders.
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