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J Allergy Clin Immunol. 2014 Dec;134(6):1394-1401.e4. doi: 10.1016/j.jaci.2014.06.029. Epub 2014 Aug 10.

"Auto-anti-IgE": naturally occurring IgG anti-IgE antibodies may inhibit allergen-induced basophil activation.

Author information

1
Department of Asthma, Allergy and Respiratory Science and Randall Division of Cell and Molecular Biophysics, King's College London; the Medical Research Council and Asthma UK Centre, Allergic Mechanisms in Asthma, London; the Department of Paediatric Allergy, Guy's and St Thomas' National Health Service Foundation Trust, London, United Kingdom.
2
Department of Asthma, Allergy and Respiratory Science and Randall Division of Cell and Molecular Biophysics, King's College London; the Medical Research Council and Asthma UK Centre, Allergic Mechanisms in Asthma, London; the Department of Paediatric Allergy, Guy's and St Thomas' National Health Service Foundation Trust, London, United Kingdom; Immunoallergology Department, Coimbra University Hospital, Coimbra, Portugal.
3
Department of Asthma, Allergy and Respiratory Science and Randall Division of Cell and Molecular Biophysics, King's College London; the Medical Research Council and Asthma UK Centre, Allergic Mechanisms in Asthma, London; the Department of Paediatric Allergy, Guy's and St Thomas' National Health Service Foundation Trust, London, United Kingdom. Electronic address: Hannah.Gould@kcl.ac.uk.

Abstract

BACKGROUND:

Naturally occurring IgE-specific IgG autoantibodies have been identified in patients with asthma and other diseases, but their spectrum of functions is poorly understood.

OBJECTIVE:

Address the hypothesis that: (i) IgG anti-IgE autoantibodies are detectable in the serum of all subjects but elevated in asthmatic patients regardless of atopic status as compared with controls; (ii) some activate IgE-sensitized basophils; and (iii) some inhibit allergen-induced basophil activation.

METHODS:

IgE-specific IgG autoantibodies were detected and quantified in sera using ELISA. Sera were examined for their ability to activate IgE-sensitized human blood basophils in the presence and absence of allergen using a basophil activation test, and to inhibit allergen binding to specific IgE on a rat basophilic cell line stably expressing human FcεRI.

RESULTS:

IgG autoantibodies binding to both free and FcεRI-bound IgE were detected in patients with atopic and non-atopic asthma, as well as controls. While some were able to activate IgE-sensitised basophils, others inhibited allergen-induced basophil activation, at least partly by inhibiting binding of IgE to specific allergen.

CONCLUSION:

Naturally occurring IgG anti-IgE autoantibodies may inhibit, as well as induce, basophil activation. They act in a manner distinct from therapeutic IgG anti-IgE antibodies such as omalizumab. They may at least partly explain why atopic subjects who make allergen-specific IgE never develop clinical symptoms, and why omalizumab therapy is of variable clinical benefit in severe atopic asthma.

KEYWORDS:

Asthma; IgE; autoantibodies; basophil activation; basophil inhibition

PMID:
25112697
PMCID:
PMC4258608
DOI:
10.1016/j.jaci.2014.06.029
[Indexed for MEDLINE]
Free PMC Article
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