title: Long-term tolerance after allergen immunotherapy is accompanied by selective persistence of blocking antibodies.
abstract: 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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Louisa K
authors.initials: LK
authors.lastname: James
authors.forename: Mohamed H
authors.initials: MH
authors.lastname: Shamji
authors.forename: Samantha M
authors.initials: SM
authors.lastname: Walker
authors.forename: Duncan R
authors.initials: DR
authors.lastname: Wilson
authors.forename: Petra A
authors.initials: PA
authors.lastname: Wachholz
authors.forename: James N
authors.initials: JN
authors.lastname: Francis
authors.forename: Mikila R
authors.initials: MR
authors.lastname: Jacobson
authors.forename: Ian
authors.initials: I
authors.lastname: Kimber
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Till
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Durham
mesh_terms: D000328:Adult; D019138:Antibodies, Blocking / Q000097:blood*; D003888:Desensitization, Immunologic; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood*; D008297:Male; D006109:Poaceae / Q000276:immunology*; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology / Q000628:therapy*; D013997:Time Factors
chemical_list: D019138:Antibodies, Blocking; D007074:Immunoglobulin G; D007073:Immunoglobulin E