When a foreign substance is introduced into the human body, the individual typically reacts by mounting an immune response by generating antibodies to this substance. A second encounter with the same substance usually elicits a faster and stronger response. In most cases, this response gives protection from the clinical course of an infection (immunity). However, the immune response is not always beneficial, as in the case where the substance provokes an antibody-mediated allergic response. About 5 to 10% of the world population suffer from allergies, and it has been estimated that 30-35 million U.S. citizens (15% of the population) suffer from at least one significant allergy.
The central molecule of the most common allergies is the antibody of the immunoglobulin E class (IgE). In terms of mass, IgE constitutes only a minute segment of total serum. Serum immunoglobulin levels of IgE are in the range of 200 nanograms (ng) per milliliter (ml), as compared to 12 mg/ml for IgG and 1 mg/ml for IgM. The low levels of IgE raises the question of its physiological function. There is evidence that IgE may play a role in the body's defense against large parasites like worms, but, if so, it is only marginally effective. Generally parasitic infections require treatment with anti-parasite drugs, and, in any case, parasites are generally not considered to be a health problem outside of third-world countries. There is no other known beneficial role of IgE.
The first step in an allergic reaction is the binding of an allergen to IgE molecules which are anchored to the surface of mast cells and basophils via specific receptors (IgE/Fc receptors). Attempts to block IgE/Fc receptors with isolated Fc fragments have been reported (Helm et al., 1989). This approach has two limitations. First, the affinity of the Fc fragment for the Fc receptor is about tenfold lower than that of an intact IgE molecule, making it necessary to administer high concentrations in order to effectively block IgE binding. Secondly, injection of this fragment at high concentrations may result in an immune response to the fragment itself. If antibodies to Fc were indeed generated, they would crosslink Fc fragments on the Fc receptors and thereby activate every mast cell and basophil. This could result in anaphylactic shock.
A second approach currently being tested is to administer antibodies which bind the Fc receptor-binding domain of the IgE molecule. These antibodies essentially absorb IgE from the circulation and prevent it from binding to mast cells and basophils. The shortcomings of this approach are (1) that the antibodies will not effectively bind IgE molecules already bound to Fc receptors, and (2) the antibodies must be administered in high doses, thus increasing the risks of complications.