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Investigators Use Sequencing Methods to Identify Triggering Allergen in Patient With EoE
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Key Takeaways
- Eosinophilic esophagitis (EoE) is an inflammatory condition triggered by multiple foods, including milk, soy, egg, and wheat.
- Researchers identified β-casein AA 59-78 as a milk protein triggering EoE using single-cell RNA sequencing and tetramer-based diagnostics.
The authors are optimistic that this method can be replicated to identify other allergens that manifest into eosinophilic esophagitis (EoE).
Research published in the Journal of Allergy and Clinical Immunology has identified one of the allergens that causes eosinophilic esophagitis (EoE), an inflammatory disease that affects the esophagus. These findings represent the first time in which research has described the molecular details of food antigen recognition in EoE, according to the investigators.1,2
Image credit: Yurii Kibalnik | stock.adobe.com
EoE is an allergic inflammatory condition that affects approximately 1 in every 2000 children, and unlike certain food allergies, EoE is one that patients do not outgrow. Rather than a single particular type of food triggering this allergic response, multiple foods—such as milk, soy, egg, and wheat—are able to activate EoE. Additionally, this disease can differ in individual patients, and what might trigger a reaction in one child might be different in another. Although there are some medications that manage allergic symptoms, such as immunosuppressants, these methods are not effective for all patients. If untreated and triggering foods are not removed from a patient’s diet, EoE can lead to scar tissue in the esophagus, putting patients at risk for food impaction.1,2
Because antigen-specific T cells have yet to be identified in a patient with EoE, the study investigators enrolled a patient with clinically established EoE milk allergy, collected the patient’s peripheral blood, and stimulated the peripheral blood mononuclear cells (PBMCs) with milk proteins. Then, a single-cell RNA sequencing was performed, with linked, paired TRA and TRB sequencing to determine the activation states and T cell receptor (TCR) clonotypes of CD4+CD45RO+ memory T helper cells that expanded in response to milk protein stimulation. Previously utilized in certain types of cancer, the tetramer-based diagnostics used 4 major histocompatibility complex molecules—which are 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.1
“The overarching goal of this project was to identify how the immune system is recognizing food antigens,” senior study author David A. Hill, MD, PhD, attending physician, Division of Allergy and Immunology at Children’s Hospital of Philadelphia, said in a news release. “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.”2
After identifying a patient with EoE who had milk as an allergic trigger, the investigators used the sequencing methods at a single cell level to pinpoint which milk protein was the cause of this patient’s case of EoE. They determined that β-casein AA 59-78 was the triggering protein.1
Further, the investigators also observed that milk-expanded peripheral T cells displayed evidence of interferon signaling. This is consistent with prior conducted research, according to the authors, and it further implicated interferons within EoE immunopathology. They also noted that the approach can provide a platform for the discovery and study of additional EoE TCRs. Expansion of this line of investigation to other subjects with EoE milk allergy is necessary to determine the composition of the milk-specific eoeTCR repertoire. This method, according to the authors, could be replicated to identify other allergens that manifest into EoE.1
“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. 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,” explained Hill in the news release.2
