Pretreatment IgE sensitization patterns determine the molecular profile of the IgG4 response during updosing of subcutaneous immunotherapy with timothy grass pollen extract

Background: Allergen immunotherapy is an effective treatment of allergic rhinoconjunctivitis. Clinical efficacy is associated with improvement of basophil sensitivity and an increase in allergen-specific immunoglobulin concentration. Objective: We sought to determine whether changes in allergen component-specific serum IgE and IgG(4) levels during the updosing phase of subcutaneous immunotherapy (SCIT) are biomarkers of the immunologic changes that can lead to treatment efficacy. Methods: Twenty-four subjects with grass pollen-induced allergic rhinoconjunctivitis were randomized 3: 1 to receive SCIT (Alutard SQ) or to an open control group. IgE and IgG(4) concentrations were determined for the major allergens Phl p 1 or Phl p 5 by using ImmunoCAP and for 8 grass pollen molecules by using Immuno Solid-phase Allergy Chip (ISAC) before treatment and after updosing. Results: Levels of specific IgE against the dominant major allergens Phl p 1 and Phl p 5 increased from a mean of 23.0 to 48.8 kU/L (P = .01, n = 18) during the updosing phase in ImmunoCAP measurements but decreased from a median of 4.6 ISAC specific units (ISU) to 2.14 ISU (P < .0001, n = 102) when measured by using ISAC against 8 grass allergen components. The updosing phase induced a specific IgG(4) level increase from a median of 0 ISU before treatment to 0.83 ISU after 12 weeks (P < .0001, n = 102) but only for allergen molecules to which pretreatment-specific IgE antibodies were detected (Spearman sigma = 0.72, P < .0001, n = 102). Conclusion: Pretreatment allergen component-specific IgE appears to determine the induction of IgG(4) in the updosing phase. Induced IgG(4) seems to suppress IgE levels on ISAC, resulting in a marked decrease in ISAC-measured specific IgE levels after updosing of SCIT. Thus this decrease in ISAC IgE levels can be used to monitor the blocking effect of allergen-specific immunotherapy-induced non-IgE antibodies.