2. Introduction:
The discovery of immunoglobulin (Ig) E in the mid-1960’ by two
independent groups led by Kimishige Ishizaka in the United States of
America and S.G.O Johansson in Sweden resulted in a significant impact
on the diagnosis and management of allergic
diseases1,2. Since then, IgE has been shown to play an
essential role in type I immediate allergic
responses3,4. Antibody isotype class switching in
favour of IgE can occur locally in the nasal mucosa5and bronchial tissues4,6,7. Dendritic cells (DCs)
present in the upper layers of the epithelium and lamina propria of the
airways8,9, gut and the skin are well disposed to
capture allergens and drive T cell polarisation towards a
pro-allergic-type II immune response. DCs migrate to the draining lymph
nodes, where they prime and activate naïve T cells to differentiate,
proliferate and clonally expand into Th2, and follicular T helper cells
that produce interleukin-4 (IL-4) and interleukin-13 (IL-13) and IL-21,
which lead to the differentiation and clonal expansion of naïve T cells
to Th2 cells. However, earlier studies demonstrating that also B cells
may be important APCs in the initiation of IgE
sensitisation10,11 are supported by more recently
published studies12,13. Moreover, the enhanced
expression of Th2 cytokines such as IL-4 and IL-13 produced by mast
cells and basophils 6,7,14 in the nasal mucosa can
promote tissue mast cells to induce IgE synthesis in B cells in an
indirect manner, resulting in local IgE synthesis by B
cells5,15. In turn, after sensitization, IgE can also
enhance Th2 cell response in a FcεRI and CD23-dependent
manner16-19. It is noteworthy that there is evidence
that (non-IgE) allergen-specific antibodies in early life can modulate
allergic sensitisation. During pregnancy and through breastmilk,
maternal immunoglobulins are transferred to offspring and it seems that
maternal allergen-specific IgG may protect the off-spring from allergic
sensitization20-22. Birth cohorts and studies in
animal models have revealed a long-term influence on offspring allergy
susceptibility21,23. Restoration of immune tolerance
following long-term allergen immunotherapy is associated with the
induction of local and systemic IgG and IgA associated neutralising
antibodies24-27
This article reviews the role of IgE, IgG and IgA in allergic
inflammation and induction of immune tolerance in early life as well as
after allergen immunotherapy. Furthermore, targeting of IgE with
anti-IgE antibodies as well as the effects of passive immunization with
allergen-specific IgG is considered and discussed.