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Hypersensitivity to mosquito bites ( HMB ) is a cutaneous disorder belonging to the group of Epstein–Barr virus ( EBV )‐associated T/natural killer ( NK )‐cell lymphoproliferative diseases, and is primarily mediated by  EBV ‐infected  NK  cells. It is characterized by intense local skin reactions accompanied by general symptoms after mosquito bites, and infiltration of  EBV ‐infected  NK  cells into the bite sites. However, the mechanisms underlying these reactions have not been fully examined. We recently described the activation of circulating basophils by mosquito extracts  in vitro  in a patient with  HMB . To further investigate this finding, we studied four additional patients with  HMB . All patients showed typical clinical features of  HMB  after mosquito bites and they had  NK  lymphocytosis and high peripheral blood  EBV DNA  loads. We found evidence of  EBV  infection in  NK  cells through  in situ  hybridization that detected  EBV ‐encoded small  RNA ‐1, and flow cytometry showed  HLA ‐ DR  expression on almost all  NK  cells. Basophil activation tests with the extracts of epidemic mosquitoes  Culex pipiens pallens  and  Aedes albopictus  showed positive responses to one or both extracts in all samples from patients with  HMB , suggesting the presence of mosquito antigen‐specific IgE and its binding to basophils. In particular, the extract of  Aedes albopictus  was able to activate basophils in all available patient samples. These results indicate that basophils and/or mast cells activated by mosquito bites may be involved in initiation and development of severe skin reactions to mosquito bites in  HMB .

Basophil activation by mosquito extracts in patients with hypersensitivity to mosquito bites