Infection with human rhinovirus 16 promotes enhanced IgE responsiveness in basophils of atopic asthmatics

BackgroundRhinovirus and IgE act in concert to promote asthma exacerbations. While basophils are the principal cell type in the blood that is activated by IgE, their role in virus-induced asthma episodes remains elusive. ObjectiveTo monitor IgE responsiveness in circulating basophils of rhinovirus-infected atopic asthmatics during acute infection and convalescence. MethodsThe capacity for basophils to respond to IgE was assessed by testing the effects of allergen, or cross-linking anti-Fc epsilon RI and anti-IgE antibodies, on surface TSLP receptor in 24-hour PBMC cultures. Activation profiles of basophils from atopic asthmatics challenged intranasally with human rhinovirus 16 were monitored directly ex vivo or else in 24-hour cultures, at baseline (day 0), and then at days 4 and 21 post-challenge. ResultsBasophils in atopic asthmatics, but not in non-atopic controls, upregulated TSLP receptor upon IgE receptor ligation. The magnitude of this response was correlated with the proportion of serum total IgE that was allergen-specific (r=0.615, P<0.05). Following rhinovirus infection, all subjects developed nasal symptoms that peaked 3-5days after viral challenge. Basophils displayed maximal IgE responsiveness 3weeks post-challenge as judged by TSLP receptor levels in 24-hour cultures. No significant change in total IgE or specific IgE antibodies was detected during rhinovirus infection. By contrast, levels of IgE receptor-associated spleen tyrosine kinase, Syk, were increased on day 4 (P<0.05), and elevated levels were also detected three weeks post-challenge. Conclusions and Clinical RelevanceCirculating basophils display increased IgE responsiveness 3weeks after rhinovirus infection in atopic asthmatics. This observation, coupled with increased expression of Syk, implicates basophils in promoting, or else prolonging, rhinovirus-induced inflammation in atopic asthmatics.