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J Allergy Clin Immunol. 2018 May;141(5):1735-1743.e9. doi: 10.1016/j.jaci.2017.07.035. Epub 2017 Sep 1.

Enhanced plasmacytoid dendritic cell antiviral responses after omalizumab.

Author information

1
Department of Pediatrics, Division of Infectious Diseases, and Immunology, University of Texas Southwestern Medical Center, Dallas, Tex; Department of Internal Medicine, Division of Allergy & Immunology, University of Texas Southwestern Medical Center, Dallas, Tex. Electronic address: Michelle.Gill@UTSouthwestern.edu.
2
Children's Hospital Colorado and the Department of Pediatrics, Division of Pulmonary Medicine, University of Colorado School of Medicine, Aurora, Colo.
3
Rho, Federal Systems Division, Chapel Hill, NC.
4
Department of Internal Medicine, Division of Allergy & Immunology, University of Texas Southwestern Medical Center, Dallas, Tex.
5
Department of Medicine, Division of Allergy & Immunology, University of Wisconsin School of Medicine and Public Health, Madison, Wis.
6
National Institute of Allergy and Infectious Diseases, Bethesda, Md.

Abstract

BACKGROUND:

Atopy and viral respiratory tract infections synergistically promote asthma exacerbations. IgE cross-linking inhibits critical virus-induced IFN-α responses of plasmacytoid dendritic cells (pDCs), which can be deficient in patients with allergic asthma.

OBJECTIVE:

We sought to determine whether reducing IgE levels in vivo with omalizumab treatment increases pDC antiviral IFN-α responses in inner-city children with asthma.

METHODS:

PBMCs 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. IFN-α levels were measured in supernatants, and mRNA expression of IFN-α pathway genes was determined by using quantitative RT-PCR (qRT-PCR) in cell pellets. FcεRIα protein levels and mRNA expression were measured in unstimulated cells by using flow cytometry and qRT-PCR, respectively. Changes in these outcomes and associations with clinical outcomes were analyzed, and statistical modeling was used to identify risk factors for asthma exacerbations.

RESULTS:

Omalizumab treatment increased rhinovirus- and influenza-induced PBMC and rhinovirus-induced pDC IFN-α responses in the presence of IgE cross-linking and reduced pDC surface FcεRIα expression. Omalizumab-induced reductions in pDC FcεRIα levels were significantly associated with a lower asthma exacerbation rate during the outcome period and correlated with increases in PBMC IFN-α responses. PBMC FcεRIα mRNA expression measured on study entry significantly improved an existing model of exacerbation prediction.

CONCLUSIONS:

These findings indicate that omalizumab treatment augments pDC IFN-α 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 asthma exacerbations.

KEYWORDS:

FcεRα; IFN-α; IgE; Plasmacytoid dendritic cells; asthma; omalizumab; rhinovirus

PMID:
28870461
PMCID:
PMC6013066
[Available on 2019-05-01]
DOI:
10.1016/j.jaci.2017.07.035

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