Scientists have identified a genetic mutation that causes a rare inherited allergy to vibration.
People with vibratory urticaria experience hives from hand clapping, towel rubbing and even running or taking a bumpy bus ride. This new study indicates that their symptoms are caused by an exaggeration of the normal response of cells to vibration.
'This work marks, to the best of our knowledge, the first identification of a genetic basis for a mast-cell-mediated urticaria induced by a mechanical stimulus,' said co-author of the study, Dr Dean Metcalfe of the National Institute of Allergy and Infectious Disease (NIAID) in Rockville, Maryland.
In the study, published in the New England Journal of Medicine, the researchers recruited three families, 36 members in all, some of whom had vibratory urticaria. The researchers found a mutation in the ADGRE2 gene in the individuals with vibratory urticaria, but not in family members without the condition. The researchers also trawled DNA databases of more than 1000 unaffected individuals with a similar genetic ancestry as the three families and did not find this particular mutation.
The researchers measured blood levels of histamine and tryptase – both markers of an allergic response – of all family members during an episode of vibration-induced urticaria, or hives. In the family members with the genetic mutation, researchers observed a rapid increase in histamine and tryptase levels. They also noted a small increase in histamine and tryptase levels in the unaffected individuals.
'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,' said Dr Hirsh Komarow, also at NIAID and senior author of the study.
The ADGRE2 mutation caused the ADGRE2 protein, which is found on the surface of mast cells, to become unstable, breaking easily into its two constituent parts and triggering the mast cells to release their contents, resulting in a classic allergic symptoms.
Director of the National Institute of Allergy and Infectious Diseases, Dr Anthony Fauci, who was not involved with the study, said: 'Investigating rare disorders such as vibratory urticaria can yield important insights into how the immune system functions and how it reacts to certain triggers to produce allergy symptoms, which can range from mild to debilitating.
'The findings from this study uncover intriguing new facets of mast cell biology, adding to our knowledge of how allergic responses occur,' he added.
The team intends to recruit more families with vibratory urticaria to look for additional mutations in ADGRE2 and other genes.