Biologics and immunotherapyEnhanced plasmacytoid dendritic cell antiviral responses after omalizumab
Section snippets
Mechanistic study design
In participants from 2 of the 8 sites of the PROSE clinical trial (UT Southwestern Medical Center, Dallas, Texas, and National Jewish Health, Denver, Colorado), blood for ex vivo assays was drawn before randomization and 12 to 16 weeks after initiation of treatment. These assays were designed to measure the effect of IgE cross-linking on virus (rhinovirus and influenza)–induced and TLR7 agonist (gardiquimod)–induced IFN-α in cultures of PBMCs (all participants) and pDCs (in a subset of
Results
IFN-α responses were evaluated in participants receiving omalizumab and placebo treatment (n = 92) at 2 clinical sites. Participants had similar demographic and laboratory characteristics as those in the multisite clinical trial, including low income, predominant Hispanic ethnicity, increased peripheral blood eosinophil counts, and total serum IgE levels (see Table E3 in this article's Online Repository at www.jacionline.org). No significant differences in baseline characteristics were found
Discussion
Overexpression of FcεRIα and cross-linking of this receptor can disrupt virus-induced IFN-α responses,5, 6 and this represents a potential mechanism for more severe viral respiratory illnesses in patients with allergic asthma. We demonstrated previously that omalizumab treatment of urban children with moderate asthma restores ex vivo PBMC IFN-α responses and that these improved responses were related to a lower risk for asthma exacerbation.10 In the present study we extend these findings by
References (32)
- et al.
Viral infections in relation to age, atopy, and season of admission among children hospitalized for wheezing
J Allergy Clin Immunol
(2004) - et al.
Innate immune responses to rhinovirus are reduced by the high-affinity IgE receptor in allergic asthmatic children
J Allergy Clin Immunol
(2012) - et al.
Human dendritic cell 1 and dendritic cell 2 subsets express FcepsilonRI: correlation with serum IgE and allergic asthma
J Allergy Clin Immunol
(2003) - et al.
Omalizumab treatment downregulates dendritic cell FcepsilonRI expression
J Allergy Clin Immunol
(2003) - et al.
Decreases in human dendritic cell-dependent T(H)2-like responses after acute in vivo IgE neutralization
J Allergy Clin Immunol
(2010) - et al.
Preseasonal treatment with either omalizumab or an inhaled corticosteroid boost to prevent fall asthma exacerbations
J Allergy Clin Immunol
(2015) - et al.
Seasonal risk factors for asthma exacerbations among inner-city children
J Allergy Clin Immunol
(2015) - et al.
Immune signaling by RIG-I-like receptors
Immunity
(2011) - et al.
Aeroallergen-induced IL-33 predisposes to respiratory virus-induced asthma by dampening antiviral immunity
J Allergy Clin Immunol
(2016) - et al.
Synergism between allergens and viruses and risk of hospital admission with asthma: case-control study
BMJ
(2002)
Study of modifiable risk factors for asthma exacerbations: virus infection and allergen exposure increase the risk of asthma hospital admissions in children
Thorax
TLR9- and FcepsilonRI-mediated responses oppose one another in plasmacytoid dendritic cells by down-regulating receptor expression
J Immunol
Counterregulation between the FcepsilonRI pathway and antiviral responses in human plasmacytoid dendritic cells
J Immunol
Cutting edge: critical role of glycolysis in human plasmacytoid dendritic cell antiviral responses
J Immunol
Predicting fall seasonal asthma exacerbations in inner-city children in the absence and presence of omalizumab therapy
J Allergy Clin Immunol
Regularization paths for generalized linear models via coordinate descent
J Stat Softw
Cited by (0)
Supported in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Department of Health and Human Services, under contract and grant numbers NIH NIAID 5R01AI098077, HHSN272200900052C, HHSN272201000052I, 1UM1AI114271-01, and UM2AI117870. Additional support was provided by the National Center for Research Resources and National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, under grants NCATS/NIH UL1TR000150, NCRR/NCAT/NIH UL1TR000077-04, UL1TR000451, UL1TR001105, UL1TR000040, UM1AI109565, UL1TR000075, 1UL1RR025780, UL1TR000154, and UL1TR001082. The following were donated: omalizumab and matching placebo by Novartis and fluticasone and matching placebo by GlaxoSmithKline under a clinical trial agreement with the University of Wisconsin-Madison; EpiPens by Mylan; and Ayr nasal rinse by B.F. Ascher & Company.
Disclosure of potential conflict of interest: M. A. Gill's institution received a grant from the National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID), consulting fees and support for travel from the American Academy of Allergy, Asthma & Immunology (AAAAI) for this work and received lecture fees from the American Academy of Pediatrics (AAP) for other works. A. H. Liu received a grant from the NIH/NIAID for this work; served on the Data Safety Monitoring Board for GlaxoSmithKline; and received speakers' fees from Merck Sharp & Dohme for other works. A. Calatroni received a grant from the NIH/NIAID for this work. R. Z. Krouse's, B. Shao's, and A. Schiltz's institutions received grants from the NIH/NIAID for this work. J. E. Gern's institution received a grant from the NIH/NIAID for this work and personally received consultancy fees from Janssen, Regeneron, and PReP Biosciences and travel expenses from Boehringer Ingelheim. W. W. Busse received a grant from the NIH/NIAID for this work; board membership from Boston Scientific and ICON; and consultancy fees from Novartis, Glaxo SmithKline, Genentech, Roche, Boehringer Ingelheim, Sanofi Genzyme, AstraZeneca, Teva, 3M, PrEPBiopharm, Circassia, Regeneron, Peptinnovate, Knopp Bio, and Elsevier. A. Togias declares no relevant conflicts of interest.