Editors' ChoiceALLERGY

Do not cross to avoid an exacerbation

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Science Translational Medicine  13 Sep 2017:
Vol. 9, Issue 407, eaao6123
DOI: 10.1126/scitranslmed.aao6123


Reducing IgE with Omalizumab in children with asthma improves the plasmacytoid dendritic cell interferon response to virus in vitro.

Asthma is a highly prevalent disease of chronic airway inflammation partially mediated by IgE. Many patients experience acute exacerbations beyond day-to-day symptom variation that prompt treatment changes. Respiratory viruses are the most common exacerbation trigger. A synergistic interaction between a viral trigger and chronic allergic inflammation is one potential mechanism for the increased inflammatory response. There is also evidence that asthmatics do not mount an appropriate interferon-mediated antiviral response, which may further potentiate an exacerbation.

Omalizumab is a monoclonal antibody that binds circulating IgE antibody. It reduces free IgE levels and IgE binding to high affinity receptors (FRI) on multiple inflammatory cell types, leading to reduced FRI cell surface expression. By reducing IgE-mediated allergic inflammation, Omalizumab reduces exacerbations in moderate to severe asthma.

Plasmacytoid dendritic cells (pDCs) are the major source of interferon-α (IFN-α) production. There is mounting evidence that IgE cross-linking of the FRI on pDCs leads to a reduction in IFN-α, which could contribute to increased asthma exacerbation severity. Gill et al. studied whether administering Omalizumab to asthmatic children in vivo could restore ex vivo pDC IFN-α responses. They isolated peripheral blood mononuclear cells (PBMC) from almost 100 children with asthma before and 12 to 16 weeks after Omalizumab treatment, and purified pDCs from about half. Omalizumab compared with placebo resulted in increased PBMC and pDC IFN-α protein expression after introduction of rhinovirus or influenza only in the presence of IgE cross- linking treatment. pDC FRI protein expression was also reduced in response to Omalizumab which correlated with asthma exacerbation rate reduction amongst Omalizumab-treated participants.

The authors suggest that restoration of pDC IFN-α production, mediated by diminished pDC FRI expression, is a potential mechanism for Omalizumab-induced asthma exacerbation reduction. The study only shows a correlative, not a causal, relationship between pDC responses and reduced exacerbation rates. The authors also discuss alternate potential mechanisms for allergic-inflammation induced inhibition of antiviral responses. Thus, the role of pDCs in exacerbations requires further investigation. However, the study does provide a promising potential mechanism for a particularly burdensome disease feature that can be reversed with treatment.

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