Proton pump inhibitors modulate esophageal epithelial barrier function and crosstalk with eosinophils.

Background: Eosinophilic esophagitis (EoE) is a chronic allergic disease characterized by esophageal dysfunction, type-2 inflammation, and esophageal eosinophilic infiltrate. While proton pump inhibitor (PPI) therapy is commonly used for EoE management, the underlying mechanism of action remains unclear.

Methods: Air-liquid interface culture of esophageal epithelial cells was employed to investigate the impact of the PPI omeprazole on barrier integrity in IL-13-treated cultures.

Advances and ongoing challenges in eosinophilic gastrointestinal disorders presented at the CEGIR/TIGERs Symposium at the 2024 American Academy of Allergy, Asthma & Immunology meeting.

The Consortium of Eosinophilic Gastrointestinal disease Researchers (CEGIR) and The International Gastrointestinal Eosinophil Researchers (TIGERs) organized a daylong symposium at the 2024 annual meeting of the American Academy of Allergy, Asthma & Immunology. The symposium featured new discoveries in basic and translational research as well as debates on the mechanisms and management of eosinophilic gastrointestinal diseases. Updates on recent clinical trials and consensus guidelines were also presented.

Pathophysiology of Eosinophilic Esophagitis.

Eosinophilic esophagitis (EoE) is a chronic, progressive immune-mediated disease associated with antigen-driven type 2 inflammation and symptoms of esophageal dysfunction. Research over the last 2 decades has dramatically furthered our understanding of the complex interplay between genetics, environmental exposures, and cellular and molecular interactions involved in EoE. This review provides an overview of our current understanding of EoE pathogenesis.

Interferon-γ signaling in eosinophilic esophagitis has implications for epithelial barrier function and programmed cell death.

Objective: Eosinophilic esophagitis (EoE) is a chronic esophageal inflammatory disorder characterized by eosinophil-rich mucosal inflammation and tissue remodeling. Transcriptional profiling of esophageal biopsies has previously revealed upregulation of type I and II interferon (IFN) response genes. We aim to unravel interactions between immune and epithelial cells and examine functional significance in esophageal epithelial cells.

Lysyl Oxidase Regulates Epithelial Differentiation and Barrier Integrity in Eosinophilic Esophagitis.

Background & Aims: Epithelial disruption in eosinophilic esophagitis (EoE) encompasses both impaired differentiation and diminished barrier integrity. We have shown that lysyl oxidase (LOX), a collagen cross-linking enzyme, is up-regulated in the esophageal epithelium in EoE. However, the functional roles of LOX in the esophageal epithelium remains unknown.

Current and future perspectives on the consensus guideline for food protein-induced enterocolitis syndrome (FPIES).

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE mediated food allergy presenting with delayed onset of projectile vomiting in the absence of cutaneous and respiratory symptoms. The pathophysiology of FPIES remains poorly characterized. The first international consensus guidelines for FPIES were published in 2017 and provided clinicians with parameters on the diagnosis and treatment of FPIES.

Persistent esophageal changes after histologic remission in eosinophilic esophagitis.

Background: Eosinophilic esophagitis (EoE) is characterized by persistent or relapsing allergic inflammation, and both clinical and histologic features of esophageal inflammation persist over time in most individuals. Mechanisms contributing to EoE relapse are not understood, and chronic EoE-directed therapy is therefore required to prevent long-term sequelae.

Objective: We investigated whether EoE patients in histologic remission have persistent dysregulation of esophageal gene expression.

Lysyl oxidase regulates epithelial differentiation and barrier integrity in eosinophilic esophagitis.

Background & Aims: Epithelial disruption in eosinophilic esophagitis (EoE) encompasses both impaired differentiation and diminished barrier integrity. We have shown that lysyl oxidase (LOX), a collagen cross-linking enzyme, is upregulated in the esophageal epithelium in EoE. However, the functional roles of LOX in the esophageal epithelium remains unknown.

Eosinophilic gastrointestinal disorders in patients with inborn errors of immunity: Data from the USIDNET registry.

Rationale: Eosinophilic gastrointestinal disorders (EGID), including eosinophilic esophagitis (EoE), are inflammatory disorders of the gastrointestinal mucosa mediated by complex immune mechanisms. Although there have been initial reports of EGID in patients with inborn errors of immunity (IEI), little is known about the presentation of EGID in immunodeficient individuals.

Methods: We queried the U.

Proton Pump Inhibitors in Allergy: Benefits and Risks.

Proton pump inhibitors (PPIs) are widely prescribed and are indicated for the treatment of several gastrointestinal disorders. Allergists may prescribe PPIs as a result of the coincidence of gastroesophageal reflux disease with asthma or rhinitis, or when gastroesophageal reflux disease presents as chronic cough. Furthermore, long-term, high-dose PPI therapy is a recommended option for managing eosinophilic esophagitis, resulting in histologic remission in approximately 40% of patients.

Adult Food Protein-Induced Enterocolitis Syndrome.

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE, cell-mediated food allergy, commonly diagnosed in infants and young children. In recent years, new-onset adult FPIES has been recognized. The underlying pathogenic mechanism of FPIES has yet to be elucidated, thus disease-specific diagnostic biomarkers have yet to be determined and an oral food challenge (OFC) remains the gold-standard for the diagnosis.

Posttreatment Gene Scores Support Histologic and Endoscopic Response Thresholds in Eosinophilic Esophagitis.

Introduction: The correlation between clinical and molecular treatment response thresholds in eosinophilic esophagitis (EoE) is not well understood.

Methods: We evaluated posttreatment EoE diagnostic panel gene expression profiles across histologic and endoscopic thresholds (EREFS) in a prospective adult EoE cohort.

Results: We observed a strong inverse correlation between posttreatment gene score and eosinophil count (R = -0.

International Consensus Recommendations for Eosinophilic Gastrointestinal Disease Nomenclature.

Background & Aims: Substantial heterogeneity in terminology used for eosinophilic gastrointestinal diseases (EGIDs), particularly the catchall term "eosinophilic gastroenteritis," limits clinical and research advances. We aimed to achieve an international consensus for standardized EGID nomenclature.

Methods: This consensus process utilized Delphi methodology.

CD73 Epithelial Progenitor Cells That Contribute to Homeostasis and Renewal Are Depleted in Eosinophilic Esophagitis.

Background & Aims: Although basal cell hyperplasia is a histologic hallmark of eosinophilic esophagitis (EoE), little is known about the capabilities of epithelial renewal and differentiation in the EoE inflammatory milieu. In murine esophageal epithelium, there are self-renewing and slowly proliferating basal stem-like cells characterized by concurrent expression of CD73 (5'-nucleotidase ecto) and CD104 (integrin β4). Here, we investigated CD73CD104 cells within the basal population of human esophageal epithelium and clarified the biological significance of these cells in the EoE epithelium.

Improvement in eosinophilic esophagitis when using dupilumab for other indications or compassionate use.

Background: Dupilumab has been approved to treat atopic dermatitis, asthma, and nasal polyps and is in active clinical trials for the treatment of eosinophilic esophagitis (EoE). Given its shared immunopathology, we hypothesized that EoE symptoms and inflammation would improve when dupilumab therapy was used for other allergic indications.

Objective: To measure the clinical and histologic response in EoE to dupilumab when treating other atopic diseases.

Medical Management of Eosinophilic Esophagitis in Pediatric Patients.

Eosinophilic esophagitis is an immune-mediated allergic disease of the esophagus that affects pediatric patients of all ages. The diagnosis is made by esophagogastroduodenoscopy demonstrating eosinophilic infiltrate of the esophagus. Approaches to treatment involve proton pump inhibitors (PPIs), swallowed topical steroid preparations, as well as dietary elimination.

RNA sequencing identifies global transcriptional changes in peripheral CD4 cells during active oesophagitis and following epicutaneous immunotherapy in eosinophilic oesophagitis.

Objective: There are no disease-modifying therapies for the treatment of eosinophilic oesophagitis (EoE), which is driven by non-IgE-mediated allergic inflammation. A recent clinical trial of milk epicutaneous immunotherapy (EPIT) has shown initial promise, with 47% of treated EoE patients tolerating milk without recurrence of disease. Mechanisms of EPIT in EoE have not been studied in humans.

Conserved IFN Signature between Adult and Pediatric Eosinophilic Esophagitis.

Eosinophilic esophagitis (EoE) is an allergic inflammatory disease of the esophagus that occurs in both children and adults. Previous studies of affected tissue from pediatric cohorts have identified prominent signatures of eosinophilia and type 2 inflammation. However, the details of the immune response in adults with EoE are still being elucidated.

The Role of Eosinophils in Immunotherapy.

Purpose Of Review: The purpose of this review is to provide a brief discussion on the differential diagnosis for peripheral eosinophilia. We will then focus on targeted immunotherapies for atopic disease, their effects on absolute peripheral eosinophil counts, and use of peripheral eosinophils as a predictor of treatment response.

Recent Findings: In atopic disease, lower absolute peripheral eosinophil counts are typically associated with improved outcomes.

The role of eosinophils in immunotherapy.

Purpose Of Review: The purpose of this review is to provide a brief discussion on the differential diagnosis for peripheral eosinophilia. We will then focus on targeted immunotherapies for atopic disease, their effects on absolute peripheral eosinophil counts, and use of peripheral eosinophils as a predictor of treatment response.

Recent Findings: In atopic disease, lower absolute peripheral eosinophil counts are typically associated with improved outcomes.