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The immune basis of the “baked egg tolerant” phenotype of egg allergy

Published online: March 5, 2018

Children with egg allergy can commonly tolerate extensively baked forms of egg. Children with tolerance to baked egg, and who incorporate baked egg into the diet, have a more rapid resolution of egg allergy compared to children who react to baked egg. Baking of egg changes the protein structure, destroys IgE binding epitopes, and reduces gastrointestinal uptake of egg proteins. However, it is not clear if the immune response to unheated egg, which contributes to persistence or resolution of egg allergy, differs between these two phenotypes of egg allergy.

In a manuscript recently published in The Journal of Allergy and Clinical Immunology (JACI), Berin and colleagues analyzed egg-specific IgE, IgG, basophil, and T cell responses in a cohort of children recruited for an egg immunotherapy study. In this multi-center study conducted by the NIAID-funded Consortium for Food Allergy Research (CoFAR), children with egg allergy were challenged at baseline to baked and unheated forms of egg. Baked egg tolerant children were randomized to receive baked egg diet or egg oral immunotherapy, and baked egg reactive children were assigned to receive egg oral immunotherapy. Baseline samples, before inclusion of any egg in the diet, were used to compare the immune responses of baked egg tolerant (n=48) versus reactive (n=81) children.

The researchers found that the baked egg reactive group had significantly higher specific IgE to egg and the egg components ovalbumin and ovomucoid. Levels of egg-specific IgG and IgG4 were higher in the baked egg tolerant group but did not reach statistical significance. Basophils stimulated with egg showed higher activation in the baked egg reactive group. Egg-specific T cells were identified by CD154 upregulation after in vitro stimulation with egg white extract. Egg-specific T cells were Th2 skewed effector cells that expressed IL-4 and IL-13 and homing molecules to support their trafficking to skin, mucosal sites, and B cell follicles. Egg-responsive CD4+ Foxp3+ Tregs were also identified. There was no significant difference in the frequency of egg-specific CD4+ T cells in the baked egg reactive and tolerant groups, however a subset of children with a high frequency of Th2 cells was observed only in the baked egg reactive group.

Although baked egg tolerance was associated with significantly lower IgE and basophil responses, the overlap between groups suggest that additional measures are needed as biomarkers of tolerance. The researchers speculate that the presence of a high frequency of Th2 cells in those with baked egg reactivity will be associated with persistence of egg allergy, which will be determined by studying these children over time.  

The Journal of Allergy and Clinical Immunology (JACI) is the official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.