It is well established that both the production of IgE by B lymphocytes and the maturation and recruitment of eosinophils in late-phase reactions are dependent on the activation of allergen-specific type-2 T-helper cells. What is less well known is the fact that efficient activation of allergen-specific T cells upon low-dose exposure to allergens is critically dependent on IgE-mediated or -facilitated allergen presentation. In fact, changes in the level of IgE-mediated allergen presentation may account for many of the immunological effects described for specific immunotherapy or anti-IgE treatment. This review aims to summarize the current knowledge, and will discuss the clinical relevance of blocking IgG antibodies induced by specific immunotherapy and anti-IgE monoclonal antibodies that both interfere with IgE-mediated allergen presentation.

We suggest that at least in birch pollen SIT, the contribution of FcgammaRIIB-mediated inhibitory signalling to SIT-IgG-induced inhibition of human basophil histamine release is of minor importance. The main contributor to the inhibitory effect of SIT-induced IgG seems to be blocking of the allergen-IgE interaction.

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Background: The role of IgG4 during allergen-specific immunotherapy (SIT) is still controversial. The available studies present paramount differences in in vitro techniques, allergens, and clinical outcome parameters. By implementing a sensitive method, and pivotal clinical outcome parameters, we wanted to ascertain the utility of IgG4 as a clinical marker of decreased allergen-specific sensitivity to a common aeroallergen. Methods: Sera were drawn from 23 birch-pollen-allergic patients during a placebo-controlled clinical trial on birch pollen SIT. Seventeen patients received active treatment. Blood samples were drawn at 0, 2, 4, 7, and 30 treatment weeks, and 36 months. The binding activity of autologous IgG, IgG4, IgE, and IgE- and/or IgG-depleted serum to ¹²⁵I-labelled recombinant Bet v 1 was assessed in a fluid-phase radioimmunoassay. Disease severity was assessed subjectively on a visual analogue scale (VAS), and objectively by intradermal late-phase reaction diameters. Results: Before SIT IgG4 fraction of IgG-allergen binding varied from 4 to 74%, with a median of 36%, increasing to 71% after 36 months. Changes in IgG4 or IgG4/IgG fraction were not correlated to clinical outcome parameters. Changes in IgG allergen binding and VAS were significantly correlated (σ = 0.72; p < 0.05). SIT increased the serum-blocking activity of IgE allergen binding from 25% before SIT to 80% after SIT. No changes were observed in the placebo group. Conclusion: The data suggest that IgG4 per se is a poor marker of decreased allergen-specific sensitivity to birch pollen, both as a single measurement and as delta values.

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