1. Introduction
Several lines of evidence support the involvement of secreted IgD in mucosal immunity. Increased serum concentrations of total IgD and allergen-specific IgD have been reported in patients with allergic respiratory diseases.1 Interestingly, symptomatic atopic individuals exhibited higher serum IgD concentrations compared to asymptomatic atopic individuals.2 However, these findings are not consistent across studies. Beekeepers with tolerance to bee venom developed higher serum levels of IgD specific for the bee venom antigen, phospholipase A2, compared with healthy controls.3 Allergen-specific IgD-producing B cells expand during allergen-specific immunotherapy, and serum levels of allergen-specific IgD correlated with asthma control3, 4. Furthermore, secreted IgD interacts with galectin-9, allowing IgD to bind to basophils and mast cells, which attenuates IgE-induced basophil degranulation. Together, these findings support the role of allergen-specific IgD in the development of allergen immune tolerance. However, ligation of basophil-bound IgD by antigen also induced basophil secretion of IL-4 and IL-13, which amplified T follicular helper type 2 cell-mediated IgG1 and IgE production by B cells.3Thus, the clinical significance of IgD in allergic disorders remains controversial.
Milk- and egg-allergic children treated with oral immunotherapy (OIT) mounted increased food antigen-specific IgD.3Moreover, ovalbumin (OVA)-specific IgD increased in desensitized egg-allergic children but not in children unresponsive to OIT or with sustained unresponsiveness to OVA challenge.3 Although egg-allergic children had higher allergen-specific IgD levels compared to the atopic controls, egg allergic children with higher levels of allergen-specific IgD had a decreased risk of anaphylactic reactions.5 However, the potential role of IgD in the development of immune tolerance to food allergens remains to be elucidated.
The natural development of tolerance and the acquisition of sustained unresponsiveness by OIT in patients with egg allergy is associated with an increase in ovomucoid (OVM)-specific IgG4 levels and a decrease in OVM-specific IgE levels.6 In this study, we determined the relationship between egg white (EW)-, OVA-, and OVM-specific IgD, IgG4 and IgE in intolerant, partially tolerant, and tolerant egg-allergic children to elucidate the role of allergen-specific IgD in the outgrowing of egg allergy.