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. IgG , IgG , IgA and IgD, may have a protective function; yet, their epitope-specific repertoires and associations with atopic comorbidities have not been studied.
Bead-Based Epitope Assay (BBEA) was used to quantitate the levels of epitope-specific (es)IgA, esIgE, esIgD, esIgG , and esIgG 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.
BBEA had high reliability (ICC>0.75) and low variability (CV<20%) and could detect known IgE-binding epitopes. Egg allergic children had lower esIgA (p=0.010) and esIgG (p=0.016) and higher esIgE (p<0.001) and esIgD (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 esIgG 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.
Collectively, these data point towards a contribution of epitope-specific antibody repertoires to the pathogenesis of egg allergy.
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