A Pilot Feasibility Study of Esophageal Antigen Test (EAT) Directed Diet versus Sham Diet for treatment of Eosinophilic Esophagitis: Novel Insights - ABSTRACT Eosinophilic esophagitis (EoE) is a chronic, antigen-driven inflammatory disease that is rapidly increasing in incidence and prevalence across all ages, races, and sexes. Uncontrolled EoE leads to painful dysphagia, progressive esophageal narrowing, and food impactions, resulting in profound reductions in quality of life and escalating healthcare costs due to repeated endoscopies required for diagnosis and monitoring. Despite this burden, only one FDA-approved treatment exists—an expensive biologic—leaving patients with few sustainable options for long-term management. Because EoE is primarily triggered by foods, dietary elimination offers a natural, cost-effective therapeutic approach that is highly desired by patients and payors alike. However, existing allergy tests lack accuracy in identifying the causal foods, forcing clinicians to rely on empiric elimination diets that require multiple endoscopies with each food reintroduction. These limitations make diet therapy cumbersome, costly, and difficult to implement in routine clinical practice. To overcome these barriers, our team has developed a novel diagnostic tool, the Esophageal Antigen Test (EAT), which detects food-specific antibodies (FSAs) within esophageal secretions obtained via a simple cytology brush. Our preliminary studies demonstrate that IgA-FSAs along the esophageal mucosa accurately identify trigger foods in EoE, outperforming skin-based allergy tests in a pilot cohort. Moreover, we have discovered that serum FSAs and kappa light chains correlate with food exposures and disease activity, suggesting their potential as non-invasive biomarkers to monitor treatment response. This proposal, directly aligned with PAS-25-102, will conduct a pilot clinical trial comparing FSA-directed (EAT-guided) elimination diets versus sham diets in patients with EoE. The study aims to: (1) determine the efficacy of IgA-FSA–guided elimination in reducing esophageal eosinophilia and symptoms compared to sham elimination; (2) assess whether serum FSAs, novel food frequency questionnaires, and kappa light chains reliably reflect food antigen exposures and disease activity; and (3) generate essential data to inform the design and sample size of future large-scale clinical trials. Our multidisciplinary team—spanning expertise in EoE, allergy, diet intervention trials, pathology, microbiome bioinformatics, Luminex-based immunoassays, and clinical nutrition—is uniquely positioned to execute this work. Successful completion of this project will optimize the EAT assay, establish serum biomarkers as feasible tools for non-invasive monitoring, and provide critical feasibility data for a future randomized trial. Ultimately, this study will transform EoE care by enabling accurate, affordable, and patient-centered dietary therapy, reducing procedural burden and healthcare costs while improving outcomes and quality of life for those affected by this debilitating disease.
