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World Allergy Forum - IgE: Bench to Bedside

Regulation and Downregulation of IgE Receptor

Donald W. MacGlashan

Since the discovery of IgE and its association with atopic diseases, it has been a goal to eliminate this subclass of antibody as a means of treating these diseases. While there remain issues concerning the role of IgE in protection from other diseases, there are nevertheless attempts to accomplish this goal by several means.

However accomplished, there are some important questions that should be asked about the requirements for successful treatment. The association of IgE antibody with the high affinity IgE receptor expressed on mast cells and basophils is a requisite for an immediate hypersensitivity reaction. The association between these two proteins is remarkably strong. IgE levels have to be quite low before occupancy of the receptor by IgE is reduced below 50%. To make matters worse, mast cells and basophils respond to antigenic challenge with very few antigen-specific IgE molecules bound to the receptor. By all appearances, this appears to be an untenable situation for the therapist.

Fortunately for the therapist, IgE antibody also regulates the expression of the receptor; reducing IgE levels also reduces receptor expression (and vice versa). This piece of receptor biology makes it more practical to reduce IgE levels as a means of controlling atopic diseases. These topics, as well as some of the newer information on high affinity IgE receptor biology, will be discussed with the goal of providing the clinician some insight into the conditions that will affect the success of any therapeutic designed to reduce IgE levels.

  1. Borkowski, T.A., et al., Minimal requirements for IgE-mediated regulation of surface Fc epsilon RI. J Immunol, 2001. 167(3): p. 1290-6.

  2. MacGlashan, D., Jr., et al., IgE-regulated loss, not IgE-regulated synthesis, controls expression of FcepsilonRI in human basophils. J Leukoc Biol, 2001. 70(2): p. 207-18.

  3. MacGlashan, D., Jr., Anti-IgE antibody therapy. Clin Allergy Immunol, 2002. 16: p. 519-32.

  4. Saini, S.S., et al., Expression and modulation of FcepsilonRIalpha and FcepsilonRIbeta in human blood basophils. J Allergy Clin Immunol, 2001. 107(5): p. 832-41.

Slide presentation

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