Shaking It — Identifying the Genetic Basis of Vibratory Urticaria

Urticaria is a generic immune response to a very wide range of stimuli, but requiring the degranulation of mast cells with resultant release of histamine. While the genetic bases for other physical urticarias have been identified, vibratory urticaria has lacked a plausible biological mechanism until now. Induced by low-frequency physical vibration of skin, these reactions cause hives, flushing, and headaches.

Three Lebanese families with autosomal dominant vibratory urticaria were analyzed using exome sequencing, utilizing prior data linking a susceptibility locus to an area of chromosome 19. Affected individuals elaborated markedly elevated levels of serum histamine in response to vibratory challenge. A mutation in ADGRE2, a G-protein coupled receptor resulting in the missense substitution at p.C492Y, appeared causative. Because urticaria depends upon the degranulation of mast cells, the authors then examined whether the presence of this mutation affected the properties of mast cells. Expression of mutant forms of ADGRE2 in a mast cell line conferred IgE-independent sensitivity to vibration in culture, with a more than twofold increase in degranulation for the mutant allele found in the families.