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Children's Hospital of Philadelphia Researchers Lead First Study to Identify Molecular Basis of Food Allergy

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PHILADELPHIA, Feb. 4, 2025 ~ A groundbreaking study led by researchers at Children's Hospital of Philadelphia (CHOP) has identified one of the allergens responsible for eosinophilic esophagitis (EoE), a chronic inflammatory disease of the esophagus. Published in the Journal of Allergy and Clinical Immunology, this is the first time that one of the allergens causing EoE has been identified at a molecular level.

EoE, a food allergy that affects approximately 1 in every 2000 children, was unknown until about 30 years ago. Unlike other food allergies, EoE is one that children do not outgrow. Instead of being triggered by a specific type of food, multiple foods such as milk, soy, egg, and wheat can cause EoE. Additionally, what may trigger this allergic response in one child may be different in another.

While some medications are available to manage allergic symptoms like immunosuppressants, they are not always effective for all patients. If left untreated and the triggering food is not removed from the diet, EoE can lead to scar tissue in the esophagus and put patients at risk for food impaction.

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The senior study author Dr. David A. Hill, an attending physician with CHOP's Division of Allergy and Immunology, explained the goal of this project: "The overarching goal of this project was to identify how the immune system is recognizing food antigens." He added that understanding this process at a molecular level could lead to better diagnostic tests and ultimately reduce the morbidity associated with EoE.

To achieve this goal, the research team used various sequencing methods including single cell RNA sequencing, T-cell receptor sequencing, and tetramer-based diagnostics. Tetramer-based diagnostics are typically used for certain types of cancer and utilize four major histocompatibility complex (MHC) molecules found on most cells in the body to identify antigen-specific T cells. This helps identify the specific antigens that trigger the immune response.

Using these methods, the researchers were able to pinpoint the exact milk protein – β-casein AA 59-78 – that caused EoE in one patient. This patient had a known allergy to milk, and the sequencing methods were able to confirm that this specific protein was responsible for their case of EoE.

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Dr. Hill emphasized that this study required collaboration and expertise from across the country, as well as advanced technology and understanding of the disease process. He also noted that while this study focused on one patient with EoE triggered by milk, their findings have broader implications and they plan to expand their research to other foods that may trigger allergic responses.

The study was supported by various grants and funds from organizations such as the American Partnership for Eosinophilic Disorders, American Academy of Allergy, Asthma, and Immunology, Food Allergy Fund, The Hartwell Foundation, Yehudai Family Foundation, and Children's Hospital of Philadelphia Endowed Chair in Genomic Research.

This groundbreaking research provides a molecular basis for understanding how food allergens are recognized in EoE. The team's findings could lead to improved diagnostic tests and potentially more effective treatments for this increasingly common childhood condition. The full study can be found online in the Journal of Allergy and Clinical Immunology with a DOI of 10.1016/j.jaci.2025.01.008.
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