Attainments in atop: special aspects of allergy and IgE

Abstract

Positive skin tests or elevated levels of specific immunoglobulin E (IgE) in the serum define IgE sensitization or "atopy." The term "allergy" refers to the clinical expression of atopic IgE-mediated disease. Genetic predisposition and decreased infections in early childhood, together with exposure and sensitization to environmental allergens, fix the basis for the elevation of IgE in infancy. Elevated IgE shortly after birth is associated with later onset of allergic disorders. IgE participates both in the immediate hypersensitivity response and in the induction of chronic allergic inflammation. The allergic response is distinct from other immune reactions in its reliance on IgE, its high-affinity receptor FcepsilonRI, and the primary effector cell-the tissue mast cell. IgE initiates the process of allergic inflammation by binding to FcepsilonRI on inflammatory cells in the airways, the gut, and the skin. Cross-linking of the IgE molecules bound to FcepsilonRI on the surface of mast cells by allergen initiates the early-phase allergic reaction. IgE bound to FcepsilonRI sets off the release of inflammatory mediators, including histamine, leukotrienes and cytokines, and leads to eosinophilic infiltration and inflammation in the affected mucosa or skin. IgE, attached to the low-affinity receptor FcepsilonRII on activated B cells and antigen-presenting cells, enhances allergen capture and type 2 helper T (Th2) cell activation, and may trigger other immunoregulatory pathways. Considerable effort in therapeutic research has focused on interference with IgE function because of its position high in the allergic cascade. Therapy with anti-IgE is one such approach that shows much promise. Large clinical studies of anti-IgE in adults and children have documented its safety and effectiveness by demonstrating the reduction of free IgE in circulation, inhibition of both early- and late-phase allergic reactions, steroid sparing, and protection against exacerbation of asthma and allergic rhinitis.