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

• Published in: Journal of allergy and clinical immunology Vol. 127; no. 2; pp. 509 - 516.e5
• Main Authors: James, Louisa K., Shamji, Mohamed H., Walker, Samantha M., Wilson, Duncan R., Wachholz, Petra A., Francis, James N., Jacobson, Mikila R., Kimber, Ian, Till, Stephen J., Durham, Stephen R.
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.02.2011; Elsevier; Elsevier Limited
• Subjects: Adult; allergens; Allergies; Allergy and Immunology; antibodies; Antibodies, Blocking - blood; Antigens; Biological activity; Biological and medical sciences; blood serum; CD23; confocal microscopy; Desensitization, Immunologic; Double-Blind Method; drug therapy; facilitated antigen presentation; Female; flow cytometry; Fundamental and applied biological sciences. Psychology; Fundamental immunology; grasses; Humans; IgE; IgG4; Immune Tolerance; immunoglobulin E; Immunoglobulin E - immunology; immunoglobulin G; Immunoglobulin G - blood; Immunopathology; Immunotherapy; Male; Medical sciences; patients; placebos; Poaceae - immunology; pollen; rhinitis; Rhinitis, Allergic, Seasonal - immunology; Rhinitis, Allergic, Seasonal - therapy; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Seasons; Time Factors; Immunotherapy; IgE; FAB; IgG4; IQR; facilitated antigen presentation; CD23; Facilitated allergen binding; Interquartile range; Immunopathology; Antigen presentation; Immunoglobulins; Desensitization; FcεRII receptor; Tolerance; Blocking antibody; Long term; Persistence; Immunology; Treatment
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2010.12.1080

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. We sought to investigate the involvement of IgG-associated inhibitory antibodies with long-term clinical tolerance after discontinuation of grass pollen immunotherapy. 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. 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. 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.