title: Combination treatment with omalizumab and rush immunotherapy for ragweed-induced allergic rhinitis: Inhibition of IgE-facilitated allergen binding.
abstract: 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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Upper Respiratory Medicine, Section of Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College London, United Kingdom.
authors.forename: Sven
authors.initials: S
authors.lastname: Klunker
authors.forename: Lavina R
authors.initials: LR
authors.lastname: Saggar
authors.forename: Vicki
authors.initials: V
authors.lastname: Seyfert-Margolis
authors.forename: Adam L
authors.initials: AL
authors.lastname: Asare
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Casale
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Durham
authors.forename: James N
authors.initials: JN
authors.lastname: Francis
mesh_terms: D000328:Adult; D031164:Ambrosia / Q000276:immunology; D018926:Anti-Allergic Agents / Q000627:therapeutic use*; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology; D052179:Antigens, Plant / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D003131:Combined Modality Therapy; D003888:Desensitization, Immunologic; D004311:Double-Blind Method; D005434:Flow Cytometry; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000187:drug effects* / Q000276:immunology; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D008875:Middle Aged; D000069444:Omalizumab; D006255:Rhinitis, Allergic, Seasonal / Q000628:therapy*
chemical_list: D018926:Anti-Allergic Agents; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D052179:Antigens, Plant; D007140:Immunoglobulin Fab Fragments; D000069444:Omalizumab; D007073:Immunoglobulin E