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

A multi-institutional study led by researchers at Children’s Hospital of Philadelphia (CHOP) is the first to identify one of the allergens responsible for eosinophilic esophagitis (EoE), an inflammatory disease of the esophagus. This is the first time one of the allergens that causes EoE has been identified at a molecular level. The findings, published today by the Journal of Allergy and Clinical Immunology, represent the first time any research team has described molecular details of food antigen recognition in EoE. The method could be replicated to identify other allergens that result in this increasingly common childhood condition.

Unknown until about 30 years ago, EoE is a food allergy that affects approximately 1 in every 2000 children, and unlike certain food allergies, EoE is one that children do not outgrow. Rather than one particular type of food triggering this allergic response, multiple foods – including milk, soy, egg and wheat – have triggered EoE. Additionally, what might trigger this reaction in one child might be different in another.

While some medications that manage allergic symptoms like immunosuppressants are prescribed, these methods are not universally effective. If left untreated and the triggering food not removed from the diet, the condition can lead to scar tissue in the esophagus, which can put patients at risk for food impaction, or when food gets trapped in the esophagus.

“The overarching goal of this project was to identify how the immune system is recognizing food antigens,” said senior study author David A. Hill, MD, PhD, an attending physician with the Division of Allergy and Immunology at CHOP. “If we understand what’s happening at a molecular level, it could allow us to develop better, more accurate diagnostic tests to find out which foods trigger this disease and ultimately reduce the morbidity associated with EoE.” 

In this study, the research team used a variety of sequencing methods, including single cell RNA sequencing, T-cell receptor sequencing and tetramer-based diagnostics. Historically used for certain types of cancer, tetramer-based diagnostics utilize four major histocompatibility complex (MHC) molecules, found on the surface of most cells in the body, to identify antigen-specific T cells, which then helps identify the antigens that trigger that T cell immune response. After identifying an EoE patient with milk as the patient’s allergic trigger, the researchers were able to use their sequencing methods at a single cell level to pinpoint which milk protein – in this case, β-casein AA 59-78 – was the cause of this patient’s case of EoE. 

“This study required expertise from across the country, as well as our advanced understanding of the disease process and the technology to approach this problem from an entirely new angle,” Hill said. “While this study focused on one patient with EoE, we believe our understanding of the molecular basis of food antigens will have much larger implications, and we’re looking to expand this research into other foods that may trigger allergic responses.”

This work was supported by an American Partnership for Eosinophilic Disorders and American Academy of Allergy, Asthma, and Immunology HOPE Grant, an American Partnership for Eosinophilic Disorders Pilot Grant, the Food Allergy Fund, The Hartwell Foundation Individual Biomedical Award, an American Academy of Allergy, Asthma, and Immunology Faculty Development Award, Institutional Development Funds from the Children’s Hospital of Philadelphia, funds from Ira & Diana Riklis and Andrew & Talia Day, the Yehudai Family Foundation, the Food Allergy Science Initiative, Institutional Development Funds from the Children’s Hospital of Philadelphia to the  Center for Applied Genomics and the Children’s Hospital of Philadelphia Endowed Chair in Genomic Research.

Dillolo et al, “A molecular basis for milk allergen immune recognition in eosinophilic esophagitis.” J Allergy Clin Immunol. Online January 31, 2025. DOI: 10.1016/j.jaci.2025.01.008.