Genetic glitch potent player in many types of allergies

Last Updated: Monday, July 29, 2013 - 22:25

Washington: Scientists have discovered that a faulty genetic pathway could be responsible for a range of allergies.

The research by the Johns Hopkins Children`s Center and the Johns Hopkins Institute of Genetic Medicine has found that aberrant signalling by a protein called transforming growth factor-beta, or TGF-beta, may be responsible for disrupting the way immune cells respond to common foods and environmental allergens, leading to a wide range of allergic disorders.

It was found that mutations in the genes that lead to abnormal TGF-beta signaling are also keys to Marfan and Loeys-Dietz syndromes, genetic conditions marked by blood vessel laxity and dangerous stretching of the aorta, the body`s largest blood vessel.

"Disruption in TGF-beta signalling does not simply nudge immune cells to misbehave but appears to singlehandedly unlock the very chain reaction that eventually leads to allergic disease," senior investigator Harry "Hal" Dietz, M.D. said.

The study involved 58 children with LDS, ages 7 to 20, followed at Johns Hopkins. Most of them had either a history of allergic disease or active allergies, like allergic rhinitis, eczema, food allergies, asthma, and gastrointestinal and esophageal allergic disease.

These patients also had abnormally high levels of several traditional markers of allergic disease, including IgE - an antibody that drives life-hreatening allergic responses - and high numbers of eosinophils, white blood cells involved in allergic reactions.

Because TGF-beta is known to control immune cell maturation, the researchers homed in on a group of cells known as regulatory T cells, which keep tabs on other immune cells to ensure that they don`t go into overdrive.

To identify precisely how TGF-beta affects immune cell behavior, the researchers next obtained undifferentiated, or naive, immune cells from LDS patients. Immersed in TGF-beta, these "pre-specialized" cells quickly transformed into allergy-promoting immune cells known for their ability to recognize and attack pathogens, as well as otherwise innocent substances, like food proteins.

In a final, critical discovery, the researchers found that the immune cells of children with LDS had abnormally high levels of a protein called SMAD, a known transmitter of TGF-beta signaling.

The study was published on July 24 in journal Science Translational Medicine.


First Published: Monday, July 29, 2013 - 22:25

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