Abstract
Immunoglobulin E (IgE)-associated allergy is the most common immunologically-mediated hypersensensitivity disease. It is based on the production of IgE antibodies and T cell responses against per se innocuous antigens (i.e., allergens) and subsequent allergen-induced inflammation in genetically pre-disposed individuals. While allergen exposure in sensitized subjects mainly boosts IgE production and T cell activation, successful allergen-specific immunotherapy (AIT) induces the production of allergen-specific IgG antibodies and reduces T cell activity. Under both circumstances, the resulting allergen-antibody complexes play a major role in modulating secondary allergen-specific immune responses: Allergen-IgE complexes induce mast cell and basophil activation and perpetuate allergen-specific T cell responses via presentation of allergen by allergen presenting cells to T cells, a process called IgE-facilitated antigen presentation (FAP). In addition, they may induce activation of IgE memory B cells. Allergen-induced production of specific IgGs usually exerts ameliorating effects but under certain circumstances may also contribute to exacerbation. Allergen-specific IgG antibodies induced by AIT which compete with IgE for allergen binding (i.e., blocking IgG) inhibit formation of IgE-allergen complexes and reduce activation of effector cells, B cells and indirectly T cells as FAP is prevented. Experimental data provide evidence that by binding of allergen-specific IgG to epitopes different from those recognized by IgE, allergen-specific IgG may enhance IgE-mediated activation of mast cells, basophils and allergen-specific IgE+ B cells. In this review we provide an overview about the role of allergen-specific antibodies in regulating secondary allergen-specific immune responses.
Highlights
30% of the world population suffer from immunoglobulin E (IgE)-associated allergy, the most common hypersensitivity disease
While the IgG repertoire seems to be broader and starting with responses to foodborne molecules in early childhood, Immunoglobulin E (IgE) is mostly directed to airborne molecules with a sequence and prevalence hierarchy. These findings indicate that IgE and IgG are raised toward different epitopes in atopic subjects
The effect of omalizumab is evident locally in target organs of allergy such as the lung: Diminished levels of CD3, CD4, CD8 lymphocytes as well as reduced staining for IgE and IL-4 were observed in the Frontiers in Immunology | www.frontiersin.org
Summary
30% of the world population suffer from immunoglobulin E (IgE)-associated allergy, the most common hypersensitivity disease. These studies confirmed reduced seasonal augmentation of allergen-specific IgE levels observed during conventional AIT In this line, hypoallergenic derivatives of birch pollen have been shown to induce protective IgG antibodies that inhibited seasonal allergen-specific IgE rises as well allergeninduced effector cell responses [97]. In the study describing the modified FAP assay, allergens were pre-incubated with sera derived from patients pre or post treatment with SIT or placebo before adding them directly to PBMCs cultures derived from the autologous patient Using this model, a significant reduction in T cell proliferation in patients undergoing AIT- compared to placebo-treated controls was observed and confirmed the importance of IgG blocking antibodies in inhibiting FAP. The effect of omalizumab is evident locally in target organs of allergy such as the lung: Diminished levels of CD3, CD4, CD8 lymphocytes as well as reduced staining for IgE and IL-4 were observed in the Frontiers in Immunology | www.frontiersin.org
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