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Scientists find faulty gene link to allergies

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(GlobalPost/GlobalPost)

US scientists said Wednesday they have found a genetic link to allergies, which also exists in people with connective tissue disorders.

The findings in the journal Science Translational Medicine show that a single genetic pathway may open the door to conditions such as asthma, food allergies and eczema.

The culprit appears to be mutations that lead to abnormal signals from a protein called transforming growth factor-beta, or TGF-beta.

When its signaling goes awry, it unleashes a "cascade of events that culminates in the development" of allergies, said lead author Pamela Frischmeyer-Guerrerio, an immunologist at Johns Hopkins Children's Center.

Researchers examined a group of 58 children with Loeys-Dietz syndrome (LDS), a connective tissue disorder that can cause an enlarged aorta and lead to aneurysm and is similar to Marfan syndrome.

Researchers noticed years ago that patients with LDS were predisposed to higher allergy rates than the general population.

LDS patients also have unusually high levels of the antibody IgE, which is a driver of allergic responses, and high counts of white blood cells known as eosinophils that are involved in allergic reactions.

Researchers found that the children's immune cells also had "abnormally high levels of a protein called SMAD, a known transmitter of TGF-beta signaling," said the study.

Among patients treated with a blood pressure drug known as losartan, this protein was reduced, suggesting the drug may offer a pathway to treating allergies.

It also signaled that heightened TGF-beta signaling was the root of the allergic response.

"Disruption in TGF-beta signaling does not simply nudge immune cells to misbehave but appears to singlehandedly unlock the very chain reaction that eventually leads to allergic disease," said senior investigator Harry Dietz, a cardiologist at Johns Hopkins Children's Center.

The researchers are currently investigating losartan's effects on allergic symptoms in animals.

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http://www.globalpost.com/dispatch/news/afp/130724/scientists-find-faulty-gene-link-allergies