Time course of serum inhibitory activity for facilitated allergen-IgE binding during bee venom immunotherapy in children

P>Background Immunotherapy for bee venom allergy is effective and provides long-term protection. Venom-specific IgG4 levels are increased but with no correlation with clinical improvement. Following grass pollen immunotherapy, elevation of antigen-specific IgG4 is accompanied by increases in IgG-dependent serum inhibitory activity for IgE-facilitated binding of allergen-IgE complexes to B cells. As this 'functional' assay of inhibitory antibodies may be more predictive of clinical efficacy, we investigated the time course of serum inhibitory activity for IgE-facilitated antigen binding during venom immunotherapy (VIT) in children and following 2 years of VIT withdrawal. Methods Ten bee venom-allergic children (mean age: 9.3 years; m/f, 7/3) with moderate to severe allergic reactions to bee stings received VIT. A separate group of seven children (mean age: 14 years; m/f, 5/2) were investigated 2 years after VIT withdrawal. Ten age- and gender-matched children served as non-allergic controls. Allergen-specific serum IgG4 and IgE levels were measured by ELISA at baseline, after 2 years of VIT and 2 years after VIT withdrawal. Serum inhibitory activity was assessed using the facilitated-allergen binding (FAB) assay. Results Sera obtained during VIT significantly inhibited allergen-IgE binding to B-cells (pre-treatment=104 +/- 23%; 2 years=46 +/- 15%; P < 0.001) when compared with sera obtained after treatment withdrawal and sera from normal controls. In parallel to FAB inhibition during VIT, significantly higher IgG4 levels were noted after immunotherapy (pre-treatment=8.6 +/- 2.3 AU; 2 years=26.7 +/- 3.5 AU; P < 0.001) compared with those observed after withdrawal and in the controls. In contrast, progressively lower IgE concentrations were observed compared with pre-treatment (44 +/- 7 AU) in sera obtained after 2 years of VIT (25 +/- 5 AU; P < 0.01) and 2 years following the withdrawal of VIT (10 +/- 3 AU; P < 0.05). Conclusions In contrast to grass pollen immunotherapy, the persistent decline in venom-specific IgE levels, rather than serum inhibitory activity for FAB, may be more relevant for long-term clinical efficacy of VIT.