A double-blind, placebo-controlled birch allergy vaccination study: inhibition of CD23-mediated serum-immunoglobulin E-facilitated allergen presentation.

ABSTRACT

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. CONCLUSION: 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.