title: Time course of serum inhibitory activity for facilitated allergen-IgE binding during bee venom immunotherapy in children.
abstract: BACKGROUND
  Immunotherapy for bee venom allergy is effective and provides long-term protection. Venom-specific IgG4 levels are increased but with no correlation with clinical improvement. Following grass pollen immunotherapy, elevation of antigen-specific IgG4 is accompanied by increases in IgG-dependent serum inhibitory activity for IgE-facilitated binding of allergen-IgE complexes to B cells. As this 'functional' assay of inhibitory antibodies may be more predictive of clinical efficacy, we investigated the time course of serum inhibitory activity for IgE-facilitated antigen binding during venom immunotherapy (VIT) in children and following 2 years of VIT withdrawal.
  
  
  METHODS
  Ten bee venom-allergic children (mean age: 9.3 years; m/f, 7/3) with moderate to severe allergic reactions to bee stings received VIT. A separate group of seven children (mean age: 14 years; m/f, 5/2) were investigated 2 years after VIT withdrawal. Ten age- and gender-matched children served as non-allergic controls. Allergen-specific serum IgG4 and IgE levels were measured by ELISA at baseline, after 2 years of VIT and 2 years after VIT withdrawal. Serum inhibitory activity was assessed using the facilitated-allergen binding (FAB) assay.
  
  
  RESULTS
  Sera obtained during VIT significantly inhibited allergen-IgE binding to B-cells (pre-treatment=104+/-23%; 2 years=46+/-15%; P<0.001) when compared with sera obtained after treatment withdrawal and sera from normal controls. In parallel to FAB inhibition during VIT, significantly higher IgG4 levels were noted after immunotherapy (pre-treatment=8.6+/-2.3 AU; 2 years=26.7+/-3.5 AU; P<0.001) compared with those observed after withdrawal and in the controls. In contrast, progressively lower IgE concentrations were observed compared with pre-treatment (44+/-7 AU) in sera obtained after 2 years of VIT (25+/-5 AU; P<0.01) and 2 years following the withdrawal of VIT (10+/-3 AU; P<0.05).
  
  
  CONCLUSIONS
  In contrast to grass pollen immunotherapy, the persistent decline in venom-specific IgE levels, rather than serum inhibitory activity for FAB, may be more relevant for long-term clinical efficacy of VIT.
authors.affiliation: Department of Paediatrics, Respiratory and Allergic Disease Division, Medical University Graz, Austria. evamaria.varga@medunigraz.at
authors.forename: E-M
authors.initials: EM
authors.lastname: Varga
authors.forename: J N
authors.initials: JN
authors.lastname: Francis
authors.forename: M S
authors.initials: MS
authors.lastname: Zach
authors.forename: S
authors.initials: S
authors.lastname: Klunker
authors.forename: W
authors.initials: W
authors.lastname: Aberer
authors.forename: S R
authors.initials: SR
authors.lastname: Durham
mesh_terms: D000293:Adolescent; D000485:Allergens / Q000008:administration & dosage* / Q000276:immunology; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D001514:Bee Venoms / Q000008:administration & dosage* / Q000276:immunology; D001516:Bees; D002648:Child; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000097:blood* / Q000276:immunology / Q000628:therapy*; D007073:Immunoglobulin E / Q000097:blood*; D007074:Immunoglobulin G / Q000097:blood* / Q000276:immunology; D007299:Insect Bites and Stings / Q000097:blood* / Q000276:immunology; D008297:Male; D013997:Time Factors
chemical_list: D000485:Allergens; D001514:Bee Venoms; D007074:Immunoglobulin G; D007073:Immunoglobulin E