Nasal allergen-neutralizing IgG4 antibodies block IgE-mediated responses: Novel biomarker of subcutaneous grass pollen immunotherapy.

Background Grass pollen subcutaneous immunotherapy (SCIT) is associated with induction of serum IgG 4 -associated inhibitory antibodies that prevent IgE-facilitated allergen binding to B cells. Objective We sought to determine whether SCIT induces nasal allergen-specific IgG 4 antibodies with inhibitory activity that correlates closely with clinical response. Methods In a cross-sectional controlled study, nasal fluid and sera were collected during the grass pollen season from 10 SCIT-treated patients, 13 untreated allergic patients (with seasonal allergic rhinitis [SAR]), and 12 nonatopic control subjects. Nasal and serum IgE and IgG 4 levels to Phleum pratense components were measured by using the Immuno Solid Allergen Chip microarray. Inhibitory activity was measured by IgE-facilitated allergen binding assay. IL-10⁺ regulatory B cells were quantified in peripheral blood by using flow cytometry. Results Nasal and serum Phl p 1– and Phl p 5–specific IgE levels were increased in patients with SAR compared to nonatopic control subjects (all, P <.001) and SCIT-treated patients (nasal, P <.001; serum Phl p 5, P =.073). Nasal IgG 4 levels were increased in the SCIT group compared to those in the SAR group (P <.001) during the pollen season compared to out of season. IgG-associated inhibitory activity in nasal fluid and serum was significantly increased in the SCIT group compared to that in the SAR (both, P <.01). The magnitude of the inhibitory activity was 93% (P <.001) in nasal fluid compared to 66% (P <.001) in serum and was reversed after depletion of IgG. Both nasal fluid (r = −0.69, P =.0005) and serum (r = −0.552, P =.0095) blocking activity correlated with global symptom improvement. IL-10⁺ regulatory B cells were increased in season compared to out of season in the SCIT group (P <.01). Conclusion For the first time, we show that nasal IgG 4 -associated inhibitory activity correlates closely with the clinical response to allergen immunotherapy in patients with allergic rhinitis with or without asthma. Graphical abstract [ABSTRACT FROM AUTHOR]