A comprehensive collaborative study has pinpointed one of the allergens linked to eosinophilic esophagitis (EoE), an inflammatory condition affecting the esophagus. This marks the first identification of a specific allergen associated with EoE at the molecular level.
A collaborative investigation spearheaded by researchers from Children’s Hospital of Philadelphia (CHOP) has successfully identified one of the allergens that lead to eosinophilic esophagitis (EoE), an inflammatory disorder of the esophagus. This discovery is groundbreaking as it is the first instance where an allergen causing EoE has been recognized at a molecular scale. The results, published today in the Journal of Allergy and Clinical Immunology, present new insights into how food antigens are recognized in EoE. This methodology may be adapted to uncover additional allergens associated with this increasingly prevalent condition in children.
Until approximately 30 years ago, EoE was not fully understood. It affects about 1 in 2,000 children and, unlike some food allergies, is not something that children typically outgrow. Various foods — such as milk, soy, eggs, and wheat — can trigger EoE, and the specific food that causes a reaction may differ from one child to another.
While there are some medications like immunosuppressants that help with allergic symptoms, they do not work for everyone. If the condition is not treated and the trigger food remains in the child’s diet, it can lead to the formation of scar tissue in the esophagus. This, in turn, increases the risk of food becoming stuck in the esophagus.
“The primary aim of this study was to understand how the immune system reacts to food antigens,” explained senior study author David A. Hill, MD, PhD, an attending physician in the Division of Allergy and Immunology at CHOP. “By grasping the molecular mechanisms involved, we could create more precise diagnostic tests to pinpoint which foods cause this illness and subsequently lower the complications related to EoE.”
In their research, the team employed various sequencing techniques, including single-cell RNA sequencing, T-cell receptor sequencing, and tetramer-based diagnostics. Traditionally used in certain cancer types, tetramer-based diagnostics leverage four major histocompatibility complex (MHC) molecules found on many body cells to identify antigen-specific T cells, facilitating the identification of the antigens that trigger this immune response. Upon identifying a patient with EoE whose allergy was linked to milk, they successfully used their sequencing methods at a single-cell level to determine that the specific milk protein responsible was β-casein AA 59-78.
“This research required collaboration from experts nationwide, along with our advanced understanding of this disease and the innovative technology to tackle the problem from a fresh perspective,” said Hill. “Although our study concentrated on one EoE patient, we believe that our insights into the molecular foundation of food antigens will have far-reaching consequences, and we’re keen to broaden our research to include other types of allergenic foods.”
This research received funding from the 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, along with Institutional Development Funds from the Children’s Hospital of Philadelphia. Additional financial contributions came from Ira & Diana Riklis, Andrew & Talia Day, the Yehudai Family Foundation, the Food Allergy Science Initiative, and dedicated funds towards the Center for Applied Genomics and the Children’s Hospital of Philadelphia Endowed Chair in Genomic Research.
