Long-term tolerance after allergen immunotherapy is accompanied by selective persistence of blocking antibodies.

Author(s): James LK, Shamji MH, Walker SM, Wilson DR, Wachholz PA, Francis JN, Jacobson MR, Kimber I, Till SJ, Durham SR

Affiliation(s): Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College London, part of the Medical Research Council and Asthma UK Centre for Allergic Mechanisms of Asthma, UK.

Publication date & source: 2011-02, J Allergy Clin Immunol., 127(2):509-516.e1-5.

Publication type: Randomized Controlled Trial; Research Support, Non-U.S. Gov't

BACKGROUND: Grass pollen immunotherapy for allergic rhinitis is a disease-modifying treatment that results in long-term clinical tolerance lasting years after treatment discontinuation. Active treatment is associated with generation of inhibitory grass pollen-specific IgG antibodies capable of blocking allergen-IgE interactions. OBJECTIVES: We sought to investigate the involvement of IgG-associated inhibitory antibodies with long-term clinical tolerance after discontinuation of grass pollen immunotherapy. METHODS: We conducted a 4-year study in which patients who had moderate-to-severe allergic rhinitis underwent a randomized, double-blind, placebo-controlled discontinuation of subcutaneous grass pollen immunotherapy. All subjects received grass pollen immunotherapy injections for 2 years (n = 13), followed by a further 2 years of either active (n = 7) or placebo (n = 6) injections. Clinical outcomes included seasonal symptoms and use of rescue medication. Serum specimens were collected at baseline and after 2 and 4 years for quantification of allergen-specific IgG antibodies. Sera were also tested for IgG-dependent inhibitory bioactivity against IgE-allergen binding in cellular assays by using flow cytometry and confocal microscopy to detect binding of IgE-grass pollen allergen complexes to B cells. RESULTS: Clinical improvement was maintained after 2 years of discontinuation. Although immunotherapy-induced grass pollen-specific IgG1 and IgG4 levels decreased to near-preimmunotherapy levels during discontinuation, inhibitory bioactivity of allergen-specific IgG antibodies was maintained unchanged. CONCLUSION: Grass pollen immunotherapy induces a subpopulation of allergen-specific IgG antibodies with potent inhibitory activity against IgE that persists after treatment discontinuation and that could account for long-term clinical tolerance. Copyright (c) 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.