If you’re happy and you know it clap your…. Damn, I’ve got hives, again.
For people with vibratory urticaria, an allergy to vibration, hanging out next to a speaker at a festival would not be the best idea. Even something as seemingly harmless as a towel drying session can result in an itchy, bumpy skin rash, sometimes alongside tiredness and even blurry vision. Having studied several families with the rare condition, scientists have now figured what drives this bizarre response at the cellular level, and the faulty gene responsible.
The research, published in the New England Journal of Medicine, began with a Lebanese family who the researchers put through a series of tests to measure responses to vibration. Members affected by the condition quickly developed skin hives at the site of stimulation, such as where items of clothing had rubbed during exercise, and blood tests showed elevated levels of histamine – a molecule released during stress and allergy. The team, from the National Institutes of Health, then used this presentation to identity a further two families with the disorder.
To find out what could be linking them together, 36 affected and unaffected members of these families had their genomes sequenced, leading the scientists to a single mutation in a gene called ADGRE2 common to only those with vibratory urticaria. The protein produced by this gene has two main parts, α and β, and is found in a variety of immune system cells, notably mast cells, which are involved in allergic reactions.
The α subunit of ADGRE2 sits on the surface of the cell, while the β portion is threaded through the cell’s outer layer, or plasma membrane. Normally, these two parts are attached and thus found in the same locations across the cell, but it seems that the mutation reduces the stability of this close interaction.
After shaking mutant mast cells in the lab, the team found that the α subunit disappeared from the surface, suggesting that the force from the vibrations disrupts their already weakened attachment. As an inhibitory molecule, its loss leaves the β portion – a signaling molecule – free to trigger a cascade of events that ultimately lead to the cell purging its pockets of inflammatory molecules, including histamine, in a process called degranulation. While this appeared to be a normal reaction to this vibratory stress in non-mutated cells, it occurred much more readily in those with the faulty ADGRE2, ultimately leading to elevated histamine levels and thus allergy symptoms.
Alongside shedding light on this intriguing disorder, the study helps to offer a wider insight into allergies in general, and could also implicate the ADGRE2 gene in other allergic reactions in which physical stimuli drive the responses. To take the work further, the team now plans on locating and examining more families with this rare condition in search of any other possible genetic contributions.