Researchers sniff out allergy genetic pathway

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.