Cytokine and antibody responses in birch-pollen-allergic patients treated with genetically modified derivatives of the major birch pollen allergen Bet v 1.
BACKGROUND
Recently, recombinant hypoallergenic derivatives of the major birch pollen allergen, Bet v 1, were used to treat birch-pollen-allergic patients in a double-blind, placebo-controlled, multi-centre immunotherapy study. The aim of this study was to evaluate the effects of vaccination with aluminium-hydroxide-adsorbed recombinant Bet v 1 derivatives versus placebo on T-cell, cytokine and antibody responses in a subgroup of patients.


METHODS
Blood was drawn from patients of the Swedish centre (n = 27; rBet v 1 fragments: n = 10; rBet v 1 trimer: n = 8, and placebo-aluminium hydroxide: n = 9) before the start and after completion of the treatment. PBMC were stimulated with rBet v 1 and analysed for cytokine (IL-4, IL-5, IL-10, IL-12, IL-13 and IFN-gamma)-secreting cells by ELISpot. Bet v 1-specific antibody levels in serum (IgG(1-4), IgE and IgA) were measured by ELISA. Skin prick tests with defined Bet v 1 concentrations were performed before and 10-11 months after the beginning of the study.


RESULTS
Bet v 1-specific IgG levels, consisting of IgG(1), IgG(2) and IgG(4), were significantly increased after treatment with recombinant allergen derivatives. Treatment with rBet v 1 trimer led to a significant (p < 0.05) reduction of Bet v 1-reactive IL-5- and IL-13-producing cells, reflecting a reduced Th2 response. In addition, a decreased number of Bet v 1-reactive IL-4 producing (p = 0.07) and an increase of IL-12-producing (p = 0.06) cells was noted in the trimer-treated patients. In contrast to placebo, active treatment resulted in significantly reduced immediate-type skin reactions to Bet v 1 even 10-11 months after treatment.


CONCLUSIONS
Vaccination with recombinant hypoallergenic Bet v 1 derivatives induces a Bet v 1-specific IgG response and leads to reduced skin reactivity in allergic patients. A reduction of Bet v 1-specific Th2 responses was observed in trimer-treated patients, which may reflect the intrinsic property of this allergen derivative.
Gafvelin
Guro
G
Clinical Immunology and Allergy Unit, Department of Medicine, Karolinska Institute and University Hospital, SE-171 76 Stockholm, Sweden. guro.gafvelin@medks.ki.se
Thunberg
Sarah
S
Kronqvist
Marianne
M
Grönlund
Hans
H
Grönneberg
Reidar
R
Troye-Blomberg
Marita
M
Akdis
Mübeccel
M
Fiebig
Helmut
H
Purohit
Ashok
A
Horak
Friedrich
F
Reisinger
Jürgen
J
Niederberger
Verena
V
Akdis
Cezmi A
CA
Cromwell
Oliver
O
Pauli
Gabrielle
G
Valenta
Rudolf
R
van Hage
Marianne
M
D000328:Adult; D000485:Allergens / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D000906:Antibodies / Q000097:blood / Q000187:drug effects* / Q000276:immunology; D029662:Betula / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood / Q000187:drug effects* / Q000276:immunology; D003888:Desensitization, Immunologic / Q000379:methods*; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000188:drug therapy* / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010940:Plant Proteins / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D011058:Pollen / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology / Q000627:therapeutic use*; D012882:Skin Tests
D000485:Allergens; D000906:Antibodies; D016207:Cytokines; D010940:Plant Proteins; D011994:Recombinant Proteins