New research uncovers molecular trigger for childhood food allergy disorder

Researchers at the Children’s Hospital of Philadelphia (CHOP) have discovered one of the food allergens responsible for eosinophilic esophagitis (EoE), a painful and persistent inflammatory disease of the oesophagus.

Published in the Journal of Allergy and Clinical Immunology, this research is the first to identify a food antigen involved in EoE at the molecular level, paving the way for improved diagnosis and treatment of the disease.

How does EoE differ from other allergies?

EoE, which was largely unknown until three decades ago, affects approximately one in every 2,000 children. Unlike some food allergies that children may outgrow, EoE persists into adulthood. The disease is triggered by various foods, including milk, soy, egg and wheat, though what might trigger this reaction in one child might be different in another. If left untreated and the suspected food not removed from the diet, EoE can cause scarring in the oesophagus, leading to complications such as food impaction — when food gets trapped in the food pipe.

“The overarching goal of this project was to identify how the immune system is recognising food antigens,” explained Dr David A. Hill, senior study author and attending physician with CHOP’s Division of Allergy and Immunology.

“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.”

A significant discovery

The research team employed a variety of sequencing techniques, including single-cell RNA sequencing, T-cell receptor sequencing and tetramer-based diagnostics. Tetramer-based diagnostics, traditionally used in cancer research, identify antigen-specific T cells by leveraging four major histocompatibility complex (MHC) molecules found on cell surfaces.

The study focused on an EoE patient with a milk allergy, using these advanced sequencing techniques to isolate the specific milk protein responsible. Researchers identified β-casein AA 59-78 as the culprit. This discovery marks a significant step forward in understanding how food allergens trigger EoE at a cellular level.

“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,” said Hill.

“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.”

The team now hope to replicate the method to identify other food allergens, potentially leading in the future to personalised treatment plans that could transform the lives of affected individuals.