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J Allergy Clin Immunol. 2017 Dec;140(6):1485-1498. doi: 10.1016/j.jaci.2017.10.010.

Mechanisms of allergen immunotherapy for inhaled allergens and predictive biomarkers.

Author information

1
Immunomodulation and Tolerance Group; Allergy and Clinical Immunology; Section of Inflammation, Repair and Development; National Heart and Lung Institute; Imperial College London, and the MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, London, United Kingdom.
2
Immunomodulation and Tolerance Group; Allergy and Clinical Immunology; Section of Inflammation, Repair and Development; National Heart and Lung Institute; Imperial College London, and the MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, London, United Kingdom. Electronic address: s.durham@imperial.ac.uk.

Abstract

Allergen immunotherapy is effective in patients with IgE-dependent allergic rhinitis and asthma. When immunotherapy is given continuously for 3 years, there is persistent clinical benefit for several years after its discontinuation. This disease-modifying effect is both antigen-specific and antigen-driven. Clinical improvement is accompanied by decreases in numbers of effector cells in target organs, including mast cells, basophils, eosinophils, and type 2 innate lymphoid cells. Immunotherapy results in the production of blocking IgG/IgG4 antibodies that can inhibit IgE-dependent activation mediated through both high-affinity IgE receptors (FcεRI) on mast cells and basophils and low-affinity IgE receptors (FcεRII) on B cells. Suppression of TH2 immunity can occur as a consequence of either deletion or anergy of antigen-specific T cells; induction of antigen-specific regulatory T cells; or immune deviation in favor of TH1 responses. It is not clear whether the altered long-term memory resides within the T-cell or the B-cell compartment. Recent data highlight the role of IL-10-producing regulatory B cells and "protective" antibodies that likely contribute to long-term tolerance. Understanding mechanisms underlying induction and persistence of tolerance should identify predictive biomarkers of clinical response and discover novel and more effective strategies for immunotherapy.

KEYWORDS:

B cells; IgE-FAB; Immunotherapy; T cells; allergic asthma; allergic rhinitis; biomarkers; long-term tolerance; mechanisms; type 2 innate lymphoid cells

PMID:
29221580
DOI:
10.1016/j.jaci.2017.10.010
[Indexed for MEDLINE]
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