Enhanced Plasmacytoid Dendritic Cell Antiviral Responses After Omalizumab

Publication date: Available online 1 September 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Michelle A. Gill, Andrew H. Liu, Agustin Calatroni, Rebecca Z. Krouse, Baomei Shao, Allison Schiltz, James E. Gern, Alkis Togias, William W. Busse
BackgroundAtopy and viral respiratory infections synergistically promote asthma exacerbations. IgE cross-linking inhibits critical viral-induced IFNα responses of plasmacytoid dendritic cells (pDCs), which can be deficient in allergic asthma.ObjectiveTo determine whether reducing IgE in vivo with omalizumab treatment increases pDC antiviral IFNα responses in inner city children with asthma.MethodsPBMCs and pDCs isolated from children with exacerbation-prone asthma before and during omalizumab treatment were stimulated ex vivo with rhinovirus and influenza in the presence or absence of IgE cross-linking. IFNα was measured in supernatants and mRNA of IFNα pathway genes determined by qRT-PCR in cell pellets. FcεRIα protein and mRNA expression were measured in unstimulated cells by flow cytometry and qRT-PCR respectively. Changes in these outcomes and associations with clinical outcomes were analyzed and statistical modeling utilized to identify risk factors for asthma exacerbations.ResultsOmalizumab treatment increased rhinovirus and influenza-induced PBMC and rhinovirus-induced pDC IFNα responses in the presence of IgE cross-linking, and reduced pDC surface FcεRIα expression. Omalizumab-induced reductions in pDC FcεRIα were significantly associated with lower asthma exacerbation rate during the outcome period and correlated with increases in PBMC IFNα responses. PBMC FcεRIα mRNA measured upon study entry significantly improved an existing model of exacerbation prediction.ConclusionsThese findings indicate that omalizumab treatment augments pDC IFNα responses and attenuates pDC FcεRIα protein expression, and provide evidence that these effects are related. These results support a potential mechanism underlying clinical observations that allergic sensitization is associated with increased susceptibility to virus-induced exacerbations of asthma.

Teaser

Omalizumab enhanced ex vivo antiviral IFNα responses and reduced pDC surface FcεRIα. Both effects were significantly associated with lower asthma exacerbation rate, highlighting a potential mechanism underlying the atopy-virus connection in promoting exacerbations of asthma.


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