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.