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Researchers sniff out allergy genetic pathway

29 July 2013
Appeared in BioNews 715

Mutations in a single genetic pathway known to be disrupted in those with connective tissue disorders have been shown to be a major cause of allergies.

Researchers studying 58 children with Loeys-Dietz syndrome (LDS), a genetic disorder affecting connective tissue, noted that they were much more likely to have severe allergies. Those with LDS and Marfan syndrome are known to have gene mutations that lead to abnormal production of a protein called transforming growth factor beta (TGFβ). These abnormal proteins are the key to the presence and severity of allergies, the team now believes.

'We have evidence that the same glitch in TGFβ 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 Dr Pamela Frischmeyer-Guerrerio, an immunologist at Johns Hopkins Children's Center and lead investigator of the study.

Allergic reactions are caused by an excessive immune response. TGFβ is known to help immune cells grow and mature, specifically regulatory T-cells. These regulatory T-cells are responsible for the control of an immune response, by suppressing activation of the immune system and preventing an overreaction. Mutations in TGFβ were found to reverse the function of the regulatory T-cells, so that instead of suppressing the immune response, they heightened it, causing more inflammation.

Dr Harry Dietz, senior investigator, said: 'Disruption in TGFβ signalling does not simply nudge immune cells to misbehave, but appears to single-handedly unlock the very chain reaction that eventually leads to allergic disease'.

The team is investigating new treatment strategies for those with allergies and immune disorders. The drug losartan, which is commonly used to treat high blood pressure, has already been shown to alleviate TGFβ signalling alterations to T-cell production and restore normal immune response.

'We're very hopeful that this will lead to a lot of new therapeutic trials', added Dr Frischmeyer-Guerrerio.

Researchers Reveal Genetic Glitch at the Root of Allergies
Newswise (press release) |  22 July 2013
Scientists discover a genetic glitch at the root of allergies
The Globe and Mail |  24 July 2013
Scientists Identify Genetic Basis Of Allergies: Treatments Could Soon Target Genes, Not Symptoms
Medical Daily |  24 July 2013
Shared Genetic Aberration Links Connective Tissue Disorders to Common Allergies
Genetic Engineering and Biotechnology News |  24 July 2013
TGFβ Receptor Mutations Impose a Strong Predisposition for Human Allergic Disease
Science Translational Medicine |  24 July 2013
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