Background Egg white proteins are usually subjected to heating, making them edible for the majority of egg-allergic children. Objective We sought to investigate the underlying mechanisms responsible for the reduced allergenicity displayed by heat-treated egg white allergens. Methods C3H/HeJ mice were orally sensitized with ovalbumin (OVA) or ovomucoid (OM) and challenged with native or heated proteins to evaluate their allergenicity. Immunoreactivity was assessed by immunoblotting using sera from egg-allergic children. In vitro gastrointestinal digestion of native and heated OVA and OM was studied by SDS-PAGE and liquid chromatography. Intestinal uptake of intact native and heated OVA and OM by human intestinal epithelial (Caco-2) cells was investigated. Rat basophil leukemia (RBL) cells passively sensitized with mouse serum and human basophils passively sensitized with egg-allergic children’s serum were used to assess the effector cell activation by heated, digested and transported OVA and OM. Results Heated OVA and OM did not induce symptoms of anaphylaxis in sensitized mice when administered orally. Heating did not completely destroy IgE-binding capacity of OVA or OM but enhanced in vitro digestibility of OVA. Digestion of both OVA and OM diminished mediator release in RBL assay and basophil activation. Heating of allergens prevented transport across human intestinal epithelial cells in a form capable of triggering basophil activation or T cell activation. Conclusions Heat treatment reduces allergenicity of OVA and OM. This is partially due to the enhanced gastrointestinal digestibility of heated OVA and the inability of heated OVA or OM to be absorbed in a form capable of triggering basophils. Clinical implications Reduced allergenicity of heated egg white proteins partially resulting from altered digestion and absorption in the gastrointestinal tract may explain the clinical tolerance of extensively heated egg in the majority of egg-allergic children. Capsule summary The majority of egg-allergic children tolerate extensively heated egg. This study demonstrates that the decreased allergenicity of heated ovalbumin and ovomucoid in large part results from altered digestion and processing in the gastrointestinal tract.

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