title: Nasal challenges with recombinant derivatives of the major birch pollen allergen Bet v 1 induce fewer symptoms and lower mediator release than rBet v 1 wild-type in patients with allergic rhinitis.
abstract: BACKGROUND
  Genetic engineering of the major birch pollen allergen (Bet v 1) has led to the generation of recombinant Bet v 1 derivatives with markedly reduced IgE-binding capacity, but with retained T cell activating ability.
  
  
  OBJECTIVE
  To compare the mucosal reactivity to rBet v 1 derivatives with rBet v 1 wild-type as basis for new therapeutic strategies for birch pollen allergy based on mucosal tolerance induction.
  
  
  METHODS
  Outside the pollen season, 10 patients with birch pollen allergic rhinitis and mild asthma underwent four nasal challenge-sessions in a randomized, double-blind, and cross-over design, employing increasing doses of rBet v 1 fragment mix, rBet v 1 trimer, rBet v 1 wild-type and diluent (albumin). Nasal lavage fluids (NAL) were collected before the challenge-series as well as 10 min, 4 and 24 h thereafter. Nasal lavage fluid levels of tryptase as well as EPO and ECP were measured as indices of mast cell and eosinophil activity, respectively.
  
  
  RESULTS
  All 10 patients tolerated the highest accumulated dose, 8.124 microg, when challenged with rBet v 1 trimer, eight with rBet v 1 fragments compared to one when challenged with rBet v 1 wild-type. No late phase reactions were observed. The change in tryptase levels (pre-challenge vs. 10 min) was significantly lower after challenges with rBet v 1 trimer and rBet v 1 fragments than with rBet v 1 wild-type. The change in EPO/ECP concentration pre-challenge versus 4 h post-challenge was lower for rBet v 1 trimer and the change was significantly lower when pre-challenge versus 24 h post-challenge to rBet v 1 fragments and rBet v 1 wild-type was examined.
  
  
  CONCLUSIONS
  The derivatives induced significantly fewer symptoms and lower mast cell and eosinophil activation than rBet v 1 wild-type upon application to the nasal mucosa. They could in the future be candidates for immunotherapy based on mucosal tolerance induction.
authors.affiliation: Department of Medicine, Division of Clinical Immunology, Karolinska Institute and Hospital, Stockholm, Sweden. marianne.van.hage-hamsten@ks.se
authors.forename: M
authors.initials: M
authors.lastname: van Hage-Hamsten
authors.forename: E
authors.initials: E
authors.lastname: Johansson
authors.forename: A
authors.initials: A
authors.lastname: Roquet
authors.forename: C
authors.initials: C
authors.lastname: Peterson
authors.forename: M
authors.initials: M
authors.lastname: Andersson
authors.forename: L
authors.initials: L
authors.lastname: Greiff
authors.forename: S
authors.initials: S
authors.lastname: Vrtala
authors.forename: R
authors.initials: R
authors.lastname: Valenta
authors.forename: R
authors.initials: R
authors.lastname: Grönneberg
mesh_terms: D000328:Adult; D000485:Allergens; D000704:Analysis of Variance; D052179:Antigens, Plant; D029662:Betula; D018592:Cross-Over Studies; D004311:Double-Blind Method; D047209:Eosinophil Peroxidase; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis; D008297:Male; D017817:Nasal Lavage Fluid / Q000737:chemistry; D009297:Nasal Mucosa / Q000201:enzymology / Q000276:immunology*; D009299:Nasal Provocation Tests; D010544:Peroxidases / Q000032:analysis; D010940:Plant Proteins; D011058:Pollen; D011994:Recombinant Proteins / Q000008:administration & dosage; D012221:Rhinitis, Allergic, Perennial / Q000201:enzymology / Q000276:immunology*; D012697:Serine Endopeptidases / Q000032:analysis; D018709:Statistics, Nonparametric; D053802:Tryptases
chemical_list: D000485:Allergens; D052179:Antigens, Plant; D018836:Inflammation Mediators; D010940:Plant Proteins; D011994:Recombinant Proteins; C061312:Bet v 1 allergen, Betula; D047209:Eosinophil Peroxidase; D010544:Peroxidases; D012697:Serine Endopeptidases; D053802:Tryptases