Ovomucoid epitope‐specific repertoire of IgE, IgG4, IgG1, IgA1, and IgD antibodies in egg‐allergic children

Abstract

Background Egg‐white ovomucoid, i.e. Gal d 1, is associated with IgE‐mediated allergic reactions in most egg allergic children. Epitope‐specific IgE levels have been correlated with the severity of egg allergy, while emerging evidence suggests that other antibodies, i.e. IgG₁, IgG₄, IgA₁ and IgD, may have a protective function; yet, their epitope‐specific repertoires and associations with atopic comorbidities have not been studied. Methods Bead‐Based Epitope Assay (BBEA) was used to quantitate the levels of epitope‐specific (es)IgA, esIgE, esIgD, esIgG₁, and esIgG₄ antibodies directed at 58 (15‐mer) overlapping peptides, covering the entire sequence of ovomucoid, in plasma of 38 egg allergic and 6 atopic children. Intraclass correlation (ICC) and coefficient of variation (CV) were used for the reliability assessment. The relationships across esIgs were evaluated using network analysis; linear and logistic regressions were used to compare groups based on egg allergy status and comorbidities. Results BBEA had high reliability (ICC>0.75) and low variability (CVesIgA₁ (p=0.010) and esIgG₁ (p=0.016) and higher esIgE (pesIgD (p=0.015) levels compared to the atopic controls. Interestingly, within the allergic group, children with higher esIgD had decreased odds of anaphylactic reactions (OR=0.48, p=0.038). Network analysis identified most associations between esIgE with either esIgG₄ or esIgD; indicating that IgE‐secreting plasma cells could originate from either sequential isotype switch from antigen‐experienced intermediate isotypes or directly from the IgD⁺ B‐cells. Conclusions Collectively, these data point towards a contribution of epitope‐specific antibody repertoires to the pathogenesis of egg allergy.