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The role of IgE, IgG, and IgA in tolerance, sensitization, and targeted treatment of allergic disease
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  • Mohamed Shamji,
  • Rudolf Valenta,
  • Theodore Jardetzky,
  • Valerie Verhasselt,
  • Stephen Durham,
  • Peter Würtzen,
  • R.J.Joost van Neeven
Mohamed Shamji
Imperial College London
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Rudolf Valenta
Medical University of Vienna, Center for Physiology and Pathophysiology
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Theodore Jardetzky
Stanford University
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Valerie Verhasselt
University of Western Australia School of Chemistry and Biochemistry
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Stephen Durham
NHLI, Imperial College
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Peter Würtzen
Alk-Abello A/S
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R.J.Joost van Neeven
Wageningen University & Research
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Abstract

Immunoglobulin E (IgE)-mediated allergy is the most common hypersensitivity disease affecting more than 30% of the population. In genetically-predisposed subjects exposure to minute quantities of allergens leads to the production of IgE antibodies which is termed allergic sensitization and mainly occurs in early childhood. Allergen-specific IgE then binds to the high (FcRI) and low affinity receptors (FcRII, also called CD23) for IgE on effector cells and antigen-presenting cells, respectively. Subsequent and repeated allergen exposure increases allergen-specific IgE levels and, by receptor cross-linking, triggers immediate release of inflammatory mediators from mast cells and basophils whereas IgE-facilitated allergen presentation perpetuates T cell-mediated allergic inflammation. Due to engagement of receptors which are highly selective for IgE even tiny amounts of allergens can induce massive inflammation. Naturally occurring allergen-specific IgG and IgA antibodies usually recognize different epitopes on allergens compared to IgE, and do not efficiently interfere with allergen-induced inflammation. However IgG and IgA antibodies to these important IgE epitopes can be induced by allergen-specific immunotherapy or by passive immunization. These will lead to competition with IgE for binding with the allergen and prevent allergic responses. Similarly, anti-IgE treatment does the same by preventing IgE from binding to its receptor on mastcells and basophils. Here we review the complex interplay of allergen-specific IgE, IgG and IgA and the corresponding cell receptors in allergic diseases and its relevance for diagnosis, treatment and prevention of allergy.

Peer review status:ACCEPTED

26 Mar 2021Submitted to Allergy
27 Mar 2021Submission Checks Completed
27 Mar 2021Assigned to Editor
28 Mar 2021Reviewer(s) Assigned
11 Apr 2021Review(s) Completed, Editorial Evaluation Pending
11 Apr 2021Editorial Decision: Revise Minor
03 May 20211st Revision Received
04 May 2021Submission Checks Completed
04 May 2021Assigned to Editor
04 May 2021Reviewer(s) Assigned
10 May 2021Review(s) Completed, Editorial Evaluation Pending
10 May 2021Editorial Decision: Accept