Reducing IgE levels as a strategy for the treatment of asthma.
IgE secretion by B lymphocytes defines the allergic state and nearly all asthmatics have higher than normal IgE levels in serum following adjustment for age and sex. It is thought that allergic mechanisms may be responsible for the increasing prevalence of asthma. In particular, in utero changes may encourage T cells to differentiate into Th2 subtypes. Th2 cells produce cytokines such as IL-4 and IL-5, which can act indirectly via B cells, mast cells and eosinophils to mediate the asthma phenotype. Alternatively, IL-4 and IL-13 may act directly on the airway. Th2 lymphocyte inflammation in asthma predisposes subjects to B cell and IgE-mediated airway inflammation. IgE binds to receptors on the surface of a variety of effector cells causing them to release a variety of mediators that promote airway hyperresponsiveness, mucus secretion and increased vascular permeability. Several strategies for decreasing IgE have been developed as a possible treatment for asthma. For example, anti-IgE monoclonal antibodies such as rhuMAb-E25 and CGP 56901 block binding of IgE to its high-affinity receptor and have been shown to reduce IgE levels in humans without causing anaphylaxis. IgE levels must be nearly completely suppressed. Recent clinical studies in subjects with asthma have shown that rhuMAb-E25 attenuates both the early and late phase responses to inhaled allergen, and reduces the associated increase in eosinophils in induced sputum. rhuMAb-E25 is well tolerated and has shown promising results in improving symptoms and lung function in patients with moderate to severe asthma. Other strategies for decreasing IgE levels include interferon gamma, IL-4 antibodies, IL-4 receptor antibodies and soluble IL-4 receptors.
Fahy
J V
JV
University of California at San Francisco, USA.
D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001249:Asthma / Q000097:blood* / Q000628:therapy*; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood*
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; C026408:anti-IgE antibodies; D007073:Immunoglobulin E