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World Allergy Organization
WAO's mission: To be a global resource and advocate in the field of allergy, advancing excellence in clinical care through education, research and training as a world-wide alliance of allergy and clinical immunology societies.

New Treatment Modalities for Allergic Disease

The Role of IgE Antibody in Allergic Diseases: New Paradigm

Judith A. Woodfolk, M.D. Ph.D.
Asthma and Allergic Diseases Center
University of Virginia, Charlottesville, VA

Summary
The association between IgE antibodies (ab) and allergic disease is well established. However, the mechanisms whereby IgE ab contributes to the pathogenesis of allergic disease and to allergic symptoms are still being elucidated. Binding of IgE ab to its high affinity receptor, FcεRI, on the surface of mast cells with subsequent release of inflammatory mediators plays a central role in the allergic inflammatory cascade. Under appropriate conditions, the dendritic cell drives the allergic response by activating Th2 effector cells. Uptake of allergens by FcεRI-bound IgE on the surface of dendritic cells targets allergen to intracellular compartments containing major histocompatibility class II molecules. This mechanism, termed antigen focusing, leads to enhanced efficiency of antigen presentation to T cells. Thus, IgE antibodies likely contribute to the allergic phenotype by diverse but complementary pathways. Though the association between IgE ab and allergic symptoms is clear, the relationship between the magnitude of IgE ab responses and disease severity is less well defined. Definition of the modified Th2 response to cat allergen (IgG4pos IgEneg ) has provided insight into the relevance of different antibody isotypes to allergic disease. Ongoing epidemiologic studies support the view that production of IgE but not IgG or IgG4 ab is a prerequisite for the development of allergic symptoms. The regulatory cytokine, IL-10, has been shown to suppress the production of IgE while enhancing IgG4 ab. However, cytokine induction in T cell cultures stimulated with allergen-derived peptides suggests a central role for IL-10 in the regulation of both IgE- and non-IgE-mediated responses. This view represents a shift in the Th1/Th2 paradigm. The development of high titer IgE ab, eg. in atopic dermatitis, could be attributed, at least in part, to IL-10 dysregulation. Multiple factors may influence regulation of the immune response to allergens including properties of the allergen itself, environment and genetics. Recent observations at the B- and T-cell level are important for advancing our understanding of the response to immunotherapy and anti-IgE therapy, and for defining immune mechanisms which drive allergic responses.

Key references

  1. Foster B, et al. Human dendritic cell 1 and dendritic cell 2 subsets express Fc, RI: Correlation with serum IgE and allergic asthma. J Allergy Clin Immunol, 2003;112:1132-1138.
  2. Maurer D, et al. Fc epsilon receptor I on dendritic cells delivers IgE-bound multivalent antigens into a cathepsin S-dependent pathway of MHC class II presentation. J Immunol 1998;161:2731-2739.
  3. Burrows B, et al. Association of asthma with serum IgE levels and skin-test reactivity to allergens. New Engl J Med, 1989;320:271-277.
  4. Cookson W. The alliance of genes and environment in asthma and allergy. (Review). Nature 1999;402:B5-B11.
  5. Akbari O, et al. Pulmonary dendritic cells producing IL-10 mediate tolerance induced by respiratory exposure to antigen. Nat Immunol 2001; 2:725-731.
  6. Platts-Mills TAE, et al. Sensitisation, asthma, and a modified Th2 response in children exposed to cat allergen: a population-based cross-sectional study. Lancet 2001;357:752-756.
  7. Reefer AJ, et al. A role for IL-10-mediated HLA-DR7-restricted T-cell dependent events in development of the modified Th2 response to cat allergen. J Immunol 2004, in press.

 

Slide presentation

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