Faulty Genes May Prove the Root Cause of Allergies

Recently published research in Science Translational Medicine shows that defective genes known to play a role in connective tissue disorders also plays a significant role in the development of allergies.

Researchers at Johns Hopkins Children’s Center and the Johns Hopkins Institute of Genetic Medicine found that people suffering from Loeys-Dietz Syndrome (LDS) also suffer a disproportionately high incidence of many allergies. Their study was based on a group of 58 children aged 7 to 20 who were diagnosed with the syndrome.

LDS is caused by mutations in the genes that encode for a specific protein, Transforming Growth Factor Beta (TGF-β.) TGF-β controls how cells grow in organs and plays a major role in regulating the immune system. Since LDS patients are highly susceptible to allergies, the researchers were looking for a possible link between TGF-β and allergies.

In short, the researchers found that the Regulatory T-Cells, responsible for suppressing inflammatory responses like those that occur with allergies, actually caused inflammatory responses in patients with LDS and those with allergies but no LDS.  They also determined that undifferentiated immune cells turned into allergy promoting immune cells when immersed in TGF-β.

“We have evidence that the same glitch in TGF-β 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,” said lead investigator Pamela Frischmeyer-Guerrerio, M.D., Ph.D., an immunologist at Johns Hopkins Children’s Center.

“Disruption in TGF-β signaling does not simply nudge immune cells to misbehave but appears to single-handedly unlock the very chain reaction that eventually leads to allergic disease,” says senior investigator Harry Dietz, M.D., professor in the McKusick-Nathans Institute of Genetic Medicine at Hopkins and director of the William S. Smilow Center for Marfan Research.

This research also found that the cells of children with LDS had high levels of a protein known as SMAD, a transmitter of  TGF-β signalling. LDS patients treated with Losartan – an older, commonly prescribed blood pressure medication known for its ability to tame TGF-β signalling – had reduced levels of the protein. For this reason, Losartan may prove to be a promising treatment for allergies.

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