A double-blind, placebo-controlled birch allergy vaccination study: inhibition of CD23-mediated serum-immunoglobulin E-facilitated allergen presentation.
BACKGROUND
The clinical efficacy of specific allergy vaccination (SAV), previously called specific immunotherapy is well documented. The working mechanism of this treatment is not completely known at present. Allergen-specific CD4+ T lymphocytes are activated at extremely low allergen concentrations in vivo possibly as a result of serum IgE-facilitated allergen presentation (S-FAP). Previously, we have shown that this process can be inhibited by long-term birch SAV sera.


METHODS
In the present study, we have analysed sera from birch-allergic patients in a randomized double-blind, placebo-controlled clinical trial for their ability to mediate S-FAP. Birch-specific IgE levels were not changed after SAV. Bet v 1-specific IgE levels, however, were significantly decreased (P<0.05) and Bet v 1-specific IgG4 levels were strongly increased after SAV (P<0.001). None of these changes were observed in the placebo group. When the sera were tested for their ability to induce S-FAP, a complete abrogation of this effect was noted in the sera from patients receiving active treatment (P<0.001), but not in the control group. This inhibition of S-FAP seemed to be associated with the reduction in the ratio between Bet v 1-specific IgE and IgG4 antibodies in serum, but a clear correlation could not be demonstrated.


CONCLUSIONS
In conclusion, the present study clearly shows that SAV leads to an inhibition of the S-FAP needed to obtain optimal T cell activation at the low allergen concentrations present in vivo. This novel mechanism may explain the increased allergen threshold levels found in allergen provocation tests and the reduction of late-phase reactions observed after SAV.
van Neerven
R J J
RJ
ALK-Abelló, Bøge Alle, Hørsholm, Denmark.
Arvidsson
M
M
Ipsen
H
H
Sparholt
S H
SH
Rak
S
S
Würtzen
P A
PA
D000485:Allergens / Q000276:immunology; D017951:Antigen Presentation; D052179:Antigens, Plant; D029662:Betula; D002478:Cells, Cultured; D003888:Desensitization, Immunologic / Q000379:methods*; D004311:Double-Blind Method; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D008213:Lymphocyte Activation; D011058:Pollen; D017455:Receptors, IgE / Q000276:immunology*; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology*; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000276:immunology
D000485:Allergens; D052179:Antigens, Plant; D007074:Immunoglobulin G; D017455:Receptors, IgE; D007073:Immunoglobulin E