Journal
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Volume 127, Issue 2, Pages 509-U1837Publisher
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2010.12.1080
Keywords
Immunotherapy; IgE; IgG4; facilitated antigen presentation; CD23
Categories
Funding
- Immune Tolerance Network
- Asthma UK
- Health Foundation
- London Law Trust
- Biotechnology and Biological Sciences Research Council (BBSRC)
- ALK-Abello
- MRC [G0200485, G0601303] Funding Source: UKRI
- Medical Research Council [G0200485, G1000758B, G0601303, G1000758] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0508-10212] Funding Source: researchfish
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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 5 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. (J Allergy Clin Immunol 2011;127:509-16.)
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