Significance of Ovomucoid- and Ovalbumin-Specific IgE/IgG4 Ratios in Egg Allergy

To determine the functional significance of immunoglobulin (Ig)G4 antibodies to ovalbumin (OVA) and ovomucoid (OVM) in egg-allergic children.Data from 117 egg-allergic children from a study of tolerance to baked egg were investigated.Tolerance to baked egg was defined by oral food challenge (OFC) and was the reference parameter. Serum antibody measurements for egg white, OVM, and OVA IgE and IgG4 were performed with the UniCAP system (Phadia US, Portage, MI). Serum mediator release assays were performed on 10 baked-egg reactive children and 9 baked-egg tolerant children by using rat basophil leukemia cells transfected with human Fcɛ receptor I. These were sensitized with human sera and then stimulated with various concentrations of egg white, OVM, and OVA followed by measurement of N-Hexosaminidase in the supernatant as a marker of mediator release.OVA- and OVM-specific IgE/IgG4 ratios were significantly higher in baked egg-reactive subjects than in those who were tolerant (P = .001 and P = .003, respectively). Adding OVA- and OVM-specific IgG4 to a model with IgE alone resulted in better prediction of baked-egg tolerance. In addition, children with severe reactions during OFC who required epinephrine had higher IgE/IgG4 ratio to OVM and/or OVA. Baked-egg reactive children also had higher mediator release, and those with higher natural log transformed IgE/IgG4 ratio to OVA were more likely to have nonzero mediator release.The balance between IgE and IgG4 to OVA and OVM has functional implications in baked-egg reactivity/tolerance. High IgE/IgG4 ratios to OVA and OVM are associated with baked-egg reactivity and anaphylaxis to baked and regular egg during OFC. Low IgE/IgG4 ratios to OVA and OVM are associated with tolerance.The implications of the role of specific IgG4 in the mechanism of tolerance is important in our understanding of food allergy. Further evaluation of food-specific IgE/IgG4 ratios is important before this can be used as clinical diagnostic tool, although the possibility is intriguing.