Ovomucoid Epitope-Specific Repertoire of IgE, IgG4, IgG1, IgA1 and IgD Antibodies in Egg-Allergic Children

Abstract

Egg allergy severity and persistence are associated with higher epitope-specific IgE levels to egg-white ovomucoid (Gal d 1) and immunoglobulin E (IgE) recognition of a larger number of sequential epitopes. Immunoglobulin G1, immunoglobulin G4, immunoglobulin A, and immunoglobulin D may protect against severe reactions; the epitope-specific repertoires of these isotypes were evaluated.In the study, researchers included 38 egg-allergic children (mean age: 6.6 years; SD: 3.6; 57% boys; 63% with anaphylaxis to egg, mean egg-specific IgE: 54 kUA/L) and 6 atopic control children (mean age: 10.6 years; SD: 3.8).A bead-based epitope assay was used to quantitate epitope-specific immunoglobulin E (esIgE), epitope-specific immunoglobulin G1 (esIgG1), epitope-specific immunoglobulin G4 (esIgG4), epitope-specific immunoglobulin A, and epitope-specific immunoglobulin D (esIgD) directed against 58 (15-mer) overlapping peptides covering the entire sequence of ovomucoid from the egg-allergic and atopic children. The relationships among epitope-specific immunoglobulins (esIgs) were evaluated by using network analysis. Linear and logistic regression were used to compare esIgs by egg allergy and allergic conditions.The bead-based epitope assay could detect known IgE-binding epitopes and had high reliability (intraclass correlation [ICC]: >0.75) and low variability (coefficient of variation [CV]: <20%); esIgE had the most variability, with 4 modules distinguished, and connected most strongly with esIgG4 or esIgD. Other esIgs were each a single group, except for a subset of esIgG1 that linked the esIgG1 and esIgD groups. Compared with atopic controls, children with egg allergy had lower epitope-specific immunoglobulin A1 (P = .010) and esIgG1 (P = .016) and higher esIgE (P < .001) and esIgD (P = .015). Adjusting for asthma and age, egg-allergic children with rhinitis had higher levels of 1 esIgG4 epitope. Adjusting for asthma, age, and esIgG1, children with egg allergy and higher esIgD had a decreased odds of anaphylactic reactions (odds ratio: 0.48; P = .038).The greater association of esIgE with either esIgG4 or esIgD suggests that esIgE may be secreted by plasma cells in a sequential isotype switch from antigen-experienced upstream isotypes (IgG4+ B cells), resulting in high-affinity IgE, or directly from IgD+ B cells, resulting in lower-affinity IgE.In this small study, the authors elucidated details of different pathways by which antibody class switching may contribute to specific IgE production, with implications for the epitope specificity, degree of ovomucoid antigen binding, and likelihood of clinical egg allergy. With these finding, the authors contribute to our understanding of why children with egg sensitization may have clinical egg allergy or be clinically tolerant.