Combination treatment with omalizumab and rush immunotherapy for ragweed-induced allergic rhinitis: Inhibition of IgE-facilitated allergen binding

• Published in: Journal of allergy and clinical immunology 2007-09, Vol.120 (3), p.688-695
• Main Authors: Klunker, Sven, PhD, Saggar, Lavina R., MSc, Seyfert-Margolis, Vicki, PhD, Asare, Adam L., PhD, Casale, Thomas B., MD, Durham, Stephen R., MD, Francis, James N., PhD
• Format: Article
• Language: English
• Subjects: Adult; Allergies; Allergy; Allergy and Immunology; Ambrosia - immunology; Anti-Allergic Agents - therapeutic use; anti-IgE; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized; Antigen Presentation - drug effects; Antigen Presentation - immunology; Antigens, Plant - immunology; B-Lymphocytes - drug effects; B-Lymphocytes - immunology; Biological and medical sciences; Cell culture; Combined Modality Therapy; Desensitization, Immunologic; Double-Blind Method; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; IgE-facilitated allergen binding; Immunoglobulin E - blood; Immunoglobulin E - drug effects; Immunoglobulin E - immunology; Immunoglobulin Fab Fragments - immunology; Immunopathology; immunotherapy; Medical research; Medical sciences; Middle Aged; Omalizumab; ragweed; Rhinitis, Allergic, Seasonal - therapy; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2007.05.034

Background The combination of anti-IgE (omalizumab) therapy with ragweed injection immunotherapy for seasonal allergic rhinitis results in a significant reduction in systemic side effects and enhanced efficacy compared with immunotherapy alone. One proposed mechanism of immunotherapy is to induce regulatory antibodies that inhibit facilitated antigen presentation. Objectives We sought to determine whether the combination protocol has a cumulative effect on inhibition of facilitated antigen presentation both during and after discontinuation of treatment. Methods Ragweed allergen immunotherapy with and without omalizumab therapy was tested in a 4-arm, double-blind, placebo-controlled study. Flow cytometry was used to detect serum inhibitory activity for IgE-facilitated CD23-dependent allergen binding to B cells as a surrogate marker for facilitated antigen presentation. Serum ragweed-specific IgG4 was measured by means of ELISA. Results Immunotherapy alone resulted in partial inhibition of allergen-IgE binding after 5 to 19 weeks of treatment compared with baseline ( P < .01). Complete inhibition of allergen-specific IgE binding was observed in both treatment groups receiving omalizumab ( P < .001). Allergen-specific IgG4 levels were only increased after immunotherapy ( P < .05), both in the presence and absence of anti-IgE treatment. Combined treatment resulted in the induction of long-lasting inhibitory antibody function for up to 42 weeks compared with either treatment alone. Conclusion Ragweed immunotherapy induced serum regulatory antibodies that partially blocked binding of allergen-IgE complexes to B cells. Additional treatment with anti-IgE, by directly blocking IgE binding to CD23, completely inhibited allergen-IgE binding. Clinical implications The combination of ragweed immunotherapy and anti-IgE resulted in prolonged inhibition of allergen-IgE binding compared with either treatment alone, events that might contribute to enhanced efficacy.