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Mechanism found for destruction of key allergy-inducing complexes, Stanford researchers say
Date:10/28/2012

STANFORD, Calif. Researchers have learned how a man-made molecule destroys complexes that induce allergic responses a discovery that could lead to the development of highly potent, rapidly acting interventions for a host of acute allergic reactions.

The study, which will be published online Oct. 28 in Nature, was led by scientists at the Stanford University School of Medicine and the University of Bern, Switzerland.

The new inhibitor disarms IgE antibodies, pivotal players in acute allergies, by detaching the antibody from its partner in crime, a molecule called FcR. (Other mechanisms lead to slower-developing allergic reactions.)

"It would be an incredible intervention if you could rapidly disconnect IgE antibodies in the midst of an acute allergic response," said Ted Jardetzky, PhD, professor of structural biology and senior investigator for the study. It turns out the inhibitor used by the team does just that.

A myriad of allergens, ranging from ragweed pollen to bee venom to peanuts, can set off IgE antibodies, resulting in allergic reactions within seconds. The new inhibitor destroys the complex that tethers IgE to the cells responsible for the reaction, called mast cells. Severing this connection would be the holy grail of IgE-targeted allergy treatment.

The first time a potential allergen enters the body, some people respond by making allergen-specific IgE antibodies. These antibodies stick around long after the initial allergen is cleared from the body. Most of the antibodies get snagged by IgE-specific receptors called FcRs, which are exposed on the surface of mast cells. The mast cells are then primed to react the next time a person encounters the allergen.

Dissociation of this IgE-FcR interaction is a sought-after goal of allergy treatment for a good reason: IgE-coated mast cells are grenades of histamine, and re-encountering the allergen is equivalent to pulling out the clip. When an a
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Contact: Rosanne Spector
manishma@stanford.edu
650-725-5374
Stanford University Medical Center
Source:Eurekalert

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