Mysterious allergy to vibrations: gene provides clue

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Imagine clapping your hands or taking a bumpy bus ride and coming out with a rash. For some people, these activities, as well as drying their hands with a towel or running, can lead to a form of hives called vibratory urticaria.

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Vibration can trigger hives, or urticaria, in some people.

Now, scientists at the National Institutes of Health (NIH) believe they have discovered the genetic mutation that underlies this rare disorder. The findings are published online in the New England Journal of Medicine.

The results suggest that the condition, which runs in families, is an exaggerated version of a normal cellular response to vibration, in which inflammatory chemicals are released from the immune system’s mast cells.

Itchy red welts, or hives, and other allergic symptoms such as flushing, headaches, fatigue, blurry vision or a metallic taste in the mouth can then occur.

Although these symptoms normally fade within an hour, the reaction may occur several times a day.

How does an allergic reaction happen?

Certain stimuli cause mast cells in the skin and other tissues to release histamine and other inflammatory chemicals into the bloodstream and surrounding tissue. This process is known as degranulation.

Fast facts about allergies

  • In Americans aged 0-17 years, food and skin allergies increased in the 10 years up to 2009-2011
  • The likelihood of skin allergies tends to decrease with age
  • Allergies are twice as prevalent among high-income families compared with families at the poverty level.

Learn more about allergies

In some people, the stimulus can be a food or dust. In those with vibratory urticaria, it is vibration.

Researchers from the National Institute of Allergy and Infectious Diseases (NIAID) and the National Human Genome Research Institute (NHGRI), both part of the NIH, looked at three families who have experienced the disorder through several generations.

The team evaluated the first family through an ongoing study into skin allergies that are caused by a physical trigger.

They investigated the role of mast cells by measuring blood levels of histamine while a patient was experiencing an episode of vibration-induced hives.

Vibration caused histamine levels to rise quickly, but they subsided after about an hour. This implied that the mast cells had released their contents.

In addition, another marker of mast cell degradation, called tryptase, was observed in skin surrounding the affected area.

Interestingly, in people without the condition, vibration also caused a small release of blood histamine and tryptase. This suggests that the reaction is normal, but people with the inherited condition experience it more strongly than the general population.

The second family had featured in a previous study carried out at Yale University in 1981.

The NIH team obtained DNA samples from 25 members of that family, and two attended the lab for evaluation. Through this family, the scientists were able to contact a third family with similar symptoms.

The quest for genetic clues

The next step was to search for a genetic basis for the disorder. To do this, the researchers carried out DNA sequencing on 36 affected and unaffected members of the three families.

They found a single mutation in the ADGRE2 gene that was shared by family members with vibratory urticaria but not present in unaffected people.

The ADGRE2 gene provides instructions for production of ADGRE2 protein, present on the surface of several types of immune cells, including mast cells. In ADGRE2, there is a beta subunit inside the cell’s outer membrane and an alpha subunit on the outer surface of the cell.

Normally, these two subunits interact, staying close together, but in people with vibratory urticaria, the team observed a less stable interaction.

When the subunits separate, the researchers believe that the beta subunit produces signals inside mast cells that lead to degranulation. This is what leads to hives and other allergy symptoms.

This interaction appears to affect how mast cells respond to particular physical triggers. Understanding this could provide new insight into other conditions that involve mast cells.

Future research plans include finding out what happens to the alpha subunit after the vibration and understanding which cell signals provoke the degranulation.

Dr. Anthony S. Fauci, director of NAID, says:

“The findings from this study uncover intriguing new facets of mast cell biology, adding to our knowledge of how allergic responses occur.”

Dr. Dan Kastner, Ph.D., scientific director of the Intramural Research Program at NHGRI and a co-author of the study, says that the interdisciplinary work carried out in unveiling this “medical mystery” highlights the power of new genomic techniques.

Medical News Today has previously reported on research linking a newly discovered gene to asthma, eczema and hay fever.