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.