Genetic cause of rare allergy to vibration discovered

A genetic mutation responsible for a rare form of allergy induced by vibration has been identified by scientists including one of Indian-origin.
Running, hand clapping, towel drying or even taking a bumpy bus ride can cause temporary skin rashes in people with this form of inherited hives, also known as vibratory urticaria.
The findings by researchers from National Institute of Health (NIH) in US suggest that people with this disorder experience an exaggerated version of a normal cellular response to vibration.
In addition to itchy red welts at the site of vibration on the skin, people with vibratory urticaria also sometimes experience flushing, headaches, fatigue, blurry vision or a metallic taste in the mouth.

Symptoms usually disappear within an hour, but those affected may experience several episodes per day.
The study involved three families in which multiple generations experienced vibratory urticaria. Researchers evaluated the first family under an ongoing clinical protocol investigating urticarias induced by a physical trigger.

Mast cells, which reside in the skin and other tissues, release histamine and other inflammatory chemicals into the bloodstream and surrounding tissue in response to certain stimuli, a process known as degranulation.
To assess potential mast cell involvement in vibratory urticaria, researchers including Avanti Desai from NIH measured blood levels of histamine during an episode of vibration-induced hives.

Histamine levels rose rapidly in response to vibration and subsided after about an hour, indicating that mast cells had released their contents. Researchers also observed increased tryptase, another marker of mast cell degranulation, in skin around the affected area.
"This suggests that a normal response to vibration, which does not cause symptoms in most people, is exaggerated in our patients with this inherited form of vibratory urticaria," Hirsh Komarow from National Institute of Allergy and Infectious Diseases (NIAID) said.
To identify the genetic basis of the disorder, the scientists performed genetic analyses, including DNA sequencing, on 36 affected and unaffected members from the three families.

They found a single mutation in the ADGRE2 gene shared by family members with vibratory urticaria but not present in unaffected people.
People with familial vibratory urticaria produce a mutated ADGRE2 protein in which this subunit interaction is less stable, the researchers found. After vibration, the alpha subunit of the mutant protein was no longer in close contact with the beta subunit.
When the alpha subunit detaches from the beta subunit, the researchers suggest, the beta subunit produces signals inside mast cells that lead to degranulation, which causes hives and other allergy symptoms.
The findings were published in the New England Journal of Medicine.