Distinguishing benign from pathologic TH2 immunity in atopic children - 05/02/16
Abstract |
Background |
Although most children with asthma and rhinitis are sensitized to aeroallergens, only a minority of sensitized children are symptomatic, implying the underlying operation of efficient anti-inflammatory control mechanisms.
Objective |
We sought to identify endogenous control mechanisms that attenuate expression of IgE-associated responsiveness to aeroallergens in sensitized children.
Methods |
In 3 independent population samples we analyzed relationships between aeroallergen-specific IgE and corresponding allergen-specific IgG (sIgG) and associated immunophenotypes in atopic children and susceptibility to asthma and rhinitis, focusing on responses to house dust mite and grass.
Results |
Among mite-sensitized children across all populations and at different ages, house dust mite–specific IgG/IgE ratios (but not IgG4/IgE ratios) were significantly lower in children with asthma compared with ratios in those without asthma and lowest among the most severely symptomatic. This finding was mirrored by relationships between rhinitis and antibody responses to grass. Depending on age/allergen specificity, 20% to 40% of children with allergen-specific IgE (sIgE) of 0.35 kU/L or greater had negative skin test responses, and these children also expressed the high sIgG/sIgE immunophenotype. sIgG1 from these children inhibited allergen-induced IgE-dependent basophil activation in a dose-dependent fashion. Profiling of aeroallergen-specific CD4+ TH memory responses revealed positive associations between sIgG/sIgE ratios and IL-10–dependent gene signatures and significantly higher IL-10/TH2 cytokine (protein) ratios among nonsymptomatic children.
Conclusion |
In addition to its role in blocking TH2 effector activation in the late-phase allergic response, IL-10 is a known IgG1 switch factor. We posit that its production during allergen-induced memory responses contributes significantly to attenuation of inflammation through promoting IgG1-mediated damping of the FcεRI-dependent acute-phase reaction. sIgG1/sIgE balance might represent a readily accessible therapeutic target for asthma/rhinitis control.
Le texte complet de cet article est disponible en PDF.Key words : Asthma, rhinitis, IgE, IgG1, basophil activation, symptoms, regulatory T cells, IL-10
Abbreviations used : CAS, HDM, MAAS, RAINE, SAM, sIgE, sIgG, SPT, URA
Plan
The Australian studies were supported principally by a series of grants from the National Health and Medical Research Council of Australia. The United Kingdom studies were funded by UK Medical Research Council (MRC) grants G0601361 and MR/K002449/1 and the JP Moulton Charitable Foundation. |
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Disclosure of potential conflict of interest: D. Belgrave is employed by GlaxoSmithKline. B. Hales has received grants from the National Health Medical Research Council and the Telethon New Children's Hospital Research Grant, is employed by Telethon Kids Institute, and has received travel support from the National Health Medical Research Council grant review panel. A. Simpson has received grants from the Medical Research Council, the JP Moulton Charitable Foundation, the North West Lung Centre Charity, the National Institute of Health Research, and the European Union 7th Framework Programme; has received a consulting fee from ThermoFisher Scientific (Phadia; ISAC measurements in MAAS for this study were performed by ThermoFisher Scientific); has received payment for lectures from GlaxoSmithKline and Chiesi; and has received travel support from GlaxoSmithKline. A. Custovic has received grants from the Medical Research Council, the JP Moulton Charitable Foundation, the North West Lung Research Centre Charity, the European Union 7th Framework Programme, and the National Institute of Health Research; has received speakers fees from Novartis, ThermoFisher, AstraZeneca, ALK-Abelló, and GlaxoSmithKline; and has consultant arrangements with Regeneron/Sanofi. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 137 - N° 2
P. 379-387 - février 2016 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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