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

llergen makes a return visit, it binds to the pre-loaded IgE on the mast cell surface, triggering the release of inflammatory mediators including histamine that promote the allergic response. As allergy sufferers are well aware, these nasty reactions can occur within a matter of seconds. In a severe allergic response, sudden anaphylactic shock and death can be the result.

The key to actively disabling the allergic response lies in the separation of IgE from the FcRs on the surface of mast cells. But separating these dangerous couples is a tall order because their interaction is extremely stable sensitizing the mast cells for weeks. Currently available treatment using omalizumab (an anti-IgE antibody sold under the trade name Xolair) can block new interactions between IgE and FcR, but it is not designed to pry the molecules apart once they've formed a bond on the surface of a mast cell. So Xolair can dampen the allergic response, but as stated on the product's website: "Xolair is not a rescue medicine and should not be used to treat sudden asthma attacks."

While simply blocking IgE binding is helpful for some allergy sufferers, when it comes to the rapid quenching of an acute allergic response, "what you'd really like to do is get rid of it," said Jardetzky. Along with scientists at the University of Bern, his team discovered that an engineered protein inhibitor called DARPin E2-79 stripped IgE from the mast cell receptor. Using this inhibitor, "an interaction that normally lasts for hours or days in terms of its stability is stripped off in a matter of seconds," said Jardetzky.

DARPin E2-79 is one of a family of engineered inhibitors containing protein-binding regions called ankryin repeats. While Jardetzky's group was using structural biology and biophysical approaches to probe the weak spots in the IgE-FcR interaction, scientists at the University of Bern were tinkering with DARPins that dampened IgE's disastrous effects. The collabo
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Contact: Rosanne Spector
manishma@stanford.edu
650-725-5374
Stanford University Medical Center
Source:Eurekalert

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