Title |
Distinguishing benign from pathologic TH2 immunity in atopic children
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Published in |
The Journal of Allergy and Clinical Immunology, October 2015
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DOI | 10.1016/j.jaci.2015.08.044 |
Pubmed ID | |
Authors |
Patrick G. Holt, Deborah Strickland, Anthony Bosco, Danielle Belgrave, Belinda Hales, Angela Simpson, Elysia Hollams, Barbara Holt, Merci Kusel, Staffan Ahlstedt, Peter D. Sly, Adnan Custovic |
Abstract |
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. We sought to identify endogenous control mechanisms that attenuate expression of IgE-associated responsiveness to aeroallergens in sensitized children. 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. 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. 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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Romania | 1 | 7% |
Italy | 1 | 7% |
United Kingdom | 1 | 7% |
Argentina | 1 | 7% |
Unknown | 10 | 71% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 10 | 71% |
Scientists | 2 | 14% |
Science communicators (journalists, bloggers, editors) | 1 | 7% |
Practitioners (doctors, other healthcare professionals) | 1 | 7% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Germany | 1 | 2% |
Belgium | 1 | 2% |
Unknown | 63 | 97% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 12 | 18% |
Student > Ph. D. Student | 9 | 14% |
Other | 7 | 11% |
Professor | 4 | 6% |
Student > Bachelor | 4 | 6% |
Other | 11 | 17% |
Unknown | 18 | 28% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 20 | 31% |
Immunology and Microbiology | 10 | 15% |
Biochemistry, Genetics and Molecular Biology | 6 | 9% |
Agricultural and Biological Sciences | 5 | 8% |
Sports and Recreations | 2 | 3% |
Other | 3 | 5% |
Unknown | 19 | 29% |