Johns Hopkins researchers attribute array of allergies to faulty genetic pathway

A faulty genetic pathway already known for its role in some connective tissue disorders is also a potent player in many types of allergies, newly published research by investigators at the Johns Hopkins Children's Center and the Johns Hopkins Institute of Genetic Medicine reveals.

Scientists have long understood that allergies are the result of a complex interplay between environment and genes. But now, in what investigators believe is a scientific first, a single genetic pathway has been implicated in an array of allergic disorders.

A report on the study's findings, published today as the cover story in Science Translational Medicine, shows that faulty signaling by a specific 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.

The protein is known for its widespread effects in the body, from controlling how cells in various organs develop to overseeing how they communicate with one another. 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.

"We have evidence that the same glitch in TGF-beta that is responsible for some of the clinical manifestations seen in Marfan and Loeys-Dietz diseases also lies behind the cascade of events that culminates in the development of conditions like asthma, food allergies, and eczema," says lead investigator Pamela Frischmeyer-Guerrerio, an immunologist at Johns Hopkins Children's Center.

Notably, the researchers add, their experiments suggest TGF-beta is more than a mere contributor in the disease process.

"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," says senior investigator Harry "Hal" Dietz, a cardiologist at Johns Hopkins Children's Center and professor in the McKusick-Nathans Institute of Genetic Medicine at Johns Hopkins.