Mechanism Found for Destruction of Key Allergy-Inducing Complexes

Researchers have learned how a synthetic 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, 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 discovery of E2-79′s mechanism of IgE inhibition could lead to rapid discoveries from other labs as well. Now that scientists know what mechanism to look for, they may be inspired to dig back through freezers full of IgE inhibitors that were identified years ago, said Jardetzky. In the light of techniques described in this study, perhaps once-neglected inhibitors will show new promise in the treatment of allergic disease. Via Mechanism Found for Destruction of Key Allergy-Inducing Complexes

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