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Researchers Uncover the Genetic Roots Behind Rare Vibration Allergy

How a bumpy road can give some people a full-body rash.

A team of National Health Institute researchers has for the first time uncovered the genetic roots of one of the strangest allergies: vibrations. The vibration allergy, which is just as it sounds, may be quite rare, but understanding it more completely may yield important insights into the fundamental malfunctioning of immune cells in the presence of allergens. The group's findings are published in the New England Journal of Medicine.


In addition to being uncommon, the vibration allergy is not very dangerous. In most cases, the allergic response is limited to hives—the pale, prickly rash most often associated with allergic and autoimmune reactions. Other less common symptoms include headaches, blurry vision, fatigue, and flushing. The triggering vibrations are everyday things: jogging, jackhammering, riding a motorcycle, towel drying. Symptoms appear within a few minutes of exposure and are gone usually within an hour.

The vibration allergy sounds weirder than it is. What's more properly known as vibratory urticaria (urticaria = hives) is in the broader category of physical urticarias. In contrast to usually more dire allergic reactions involving a chemical trigger, like penicillin or shellfish, physical triggers include everyday things like heat, cold, pressure, sweating, and exercise. As a kid, I'd sometimes wind up with intensely itchy full-body hives after gym class. It sucked, but not nearly as bad as having my throat close up because of a strawberry.

The NIH group, led by allergist Hirsh Komarow, had only three families to work with—36 subjects in all. The families each had multiple generations that experienced the vibration allergy, but not all members of the families had the allergy. This was important as it allowed the researches to root out genetic mutations present in the vibration-allergic group but not in the the non-allergic group. The culprit turned out to be a shared mutation in the ADGRE2 gene.


Mast cell. Image: Yale

As Komarow and his group explain, it's this mutation that allows for the triggering of the immune response via a "purely mechanical means." The ADGRE2 gene encodes for a protein of the same name, which is found on the surfaces of cells known as mast cells—white blood cells responsible for the release of histamine, the compound behind localized immune activity and which plays a key role in the immune system's inflammatory response.

The ADGRE2 protein consists of two chemically bound subunits. The alpha subunit is located on the outside surface of mast cell while the beta subunit is located within the cellular membrane itself. As explained in current study, the interaction between these two subunits has a not-very-well-understood role in normal immune system functioning, but the ADGRE2 genetic mutation predisposes the two protein subunits to coming apart when they're not supposed to, such as in the presence of normal vibration. The vibration causes a shear force, which causes the subunits to separate or cleave.

What happens next is "aberrant degranulation" within the mast cells. Basically, these cells feature various immunoactive compounds which are stored in tiny vesicles called granules within the cells. When the cells get the right signal, the granules start sticking to the surrounding cellular membrane, with the result being the release of their contents into the outside world. Such contents may include histamine.

While the vibration allergy may be rare, the process by which the ADGRE2 alpha and beta subunits mediate immune system reactions has implications for everyone. Mast cells play a central role in immune system activity, generally: autoimmune diseases, allergic reactions, and normal physiological responses to pathogens. Understanding the process of degranulation thus means better understanding how the body fights off outside invaders in the very first place.