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.