Ovomucoid epitope‐specific repertoire of IgE, IgG 4 , IgG 1 , IgA 1 , and IgD antibodies in egg‐allergic children

Background Egg‐white ovomucoid, that is, 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 antibody isotypes (IgG 1 , IgG 4 , IgA, 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, es IgE, es IgD, es IgG 1 , and es IgG 4 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 es Igs 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 (CV <20%) and could detect known IgE‐binding epitopes. Egg‐allergic children had lower es IgA 1 ( P  = .010) and es IgG 1 ( P  = .016) and higher es IgE ( P  < .001) and es IgD ( P  = .015) levels compared to the atopic controls. Interestingly, within the allergic group, children with higher es IgD had decreased odds of anaphylactic reactions (OR =0.48, P  = .038). Network analysis identified most associations between es IgE with either es IgG 4 or es IgD; 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 toward a contribution of epitope‐specific antibody repertoires to the pathogenesis of egg allergy.