title: Infection with human rhinovirus 16 promotes enhanced IgE responsiveness in basophils of atopic asthmatics.
abstract: BACKGROUND
  Rhinovirus 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.
  
  
  OBJECTIVE
  To monitor IgE responsiveness in circulating basophils of rhinovirus-infected atopic asthmatics during acute infection and convalescence.
  
  
  METHODS
  The capacity for basophils to respond to IgE was assessed by testing the effects of allergen, or cross-linking anti-FcεRI 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.
  
  
  RESULTS
  Basophils 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 3-5 days after viral challenge. Basophils displayed maximal IgE responsiveness 3 weeks 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
  Circulating basophils display increased IgE responsiveness 3 weeks 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.
authors.affiliation: Department of Medicine, University of Virginia Health System, Charlottesville, VA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Agrawal
authors.forename: J
authors.initials: J
authors.lastname: Wisniewski
authors.forename: M D
authors.initials: MD
authors.lastname: Yu
authors.forename: J L
authors.initials: JL
authors.lastname: Kennedy
authors.forename: T
authors.initials: T
authors.lastname: Platts-Mills
authors.forename: P W
authors.initials: PW
authors.lastname: Heymann
authors.forename: J A
authors.initials: JA
authors.lastname: Woodfolk
mesh_terms: D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000276:immunology*; D001491:Basophils / Q000276:immunology*; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood*; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis; D008875:Middle Aged; D010850:Picornaviridae Infections / Q000276:immunology*; D011505:Protein-Tyrosine Kinases / Q000032:analysis; D018121:Receptors, Cytokine / Q000032:analysis; D012229:Rhinovirus / Q000276:immunology*; D000072377:Syk Kinase; D060149:Tetraspanin 30 / Q000032:analysis
chemical_list: C554586:CD63 protein, human; C498762:CRLF2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D018121:Receptors, Cytokine; D060149:Tetraspanin 30; D007073:Immunoglobulin E; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase
keywords: IgE; Syk; TSLP receptor; asthma; basophils; rhinovirus
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