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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

van Hage-Hamsten, M; Johansson, E; Roquet, A; Peterson, C; Andersson, Morgan LU ; Greiff, Lennart LU ; Vrtala, S; Valenta, R and Gronneberg, R (2002) In Clinical and Experimental Allergy 32(10). p.1448-1453
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... (More)
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 mug, 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. Conclusion 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
recombinant, nasal challenge, mucosa, ECP, Bet v 1, birch pollen, tryptase, hypoallergenic derivatives
in
Clinical and Experimental Allergy
volume
32
issue
10
pages
1448 - 1453
publisher
Wiley-Blackwell
external identifiers
  • pmid:12372124
  • wos:000178479300011
  • scopus:0036413238
ISSN
1365-2222
DOI
10.1046/j.1365-2745.2002.01495.x
language
English
LU publication?
yes
id
4aa8ed70-4479-4d44-89f6-3f8359ea3041 (old id 326199)
date added to LUP
2007-11-09 14:45:28
date last changed
2017-11-05 03:28:47
@article{4aa8ed70-4479-4d44-89f6-3f8359ea3041,
  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 mug, 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. Conclusion 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.},
  author       = {van Hage-Hamsten, M and Johansson, E and Roquet, A and Peterson, C and Andersson, Morgan and Greiff, Lennart and Vrtala, S and Valenta, R and Gronneberg, R},
  issn         = {1365-2222},
  keyword      = {recombinant,nasal challenge,mucosa,ECP,Bet v 1,birch pollen,tryptase,hypoallergenic derivatives},
  language     = {eng},
  number       = {10},
  pages        = {1448--1453},
  publisher    = {Wiley-Blackwell},
  series       = {Clinical and Experimental Allergy},
  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},
  url          = {http://dx.doi.org/10.1046/j.1365-2745.2002.01495.x},
  volume       = {32},
  year         = {2002},
}