Nasal allergen‐neutralizing antibodies correlate closely with tolerated intranasal allergen challenge dose following grass pollen subcutaneous immunotherapy in patients with local allergic rhinitis

Background Local allergic rhinitis (LAR) is defined by chronic nasal symptoms, absence of atopy, positive nasal allergen challenge (NAC) and a good response to subcutaneous allergen immunotherapy (SCIT). We sought to investigate SCIT capacity to induce local and systemic blocking antibodies in LAR patients. Methods A RDBPC study of grass SCIT was performed, with participants receiving either SCIT (Group A; n = 10) or placebo (Group B; n = 14) in the first 6 months. Both groups subsequently received SCIT for 12 months at Year 2. Nasal and serum antibodies (IgG4, IgA1 and IgA2) and their inhibitory capacity were measured at multiple timepoints. Results The allergen concentration tolerated increased significantly at 6 months (Group A; p = .047) and 24 months (Group B; p = .049) compared with baseline and persisted until the end of the study. Induction of serum sIgA1 to Phl p was seen in Groups A and B, albeit the former being induced earlier (1.71‐fold, p = .027). A significant induction in sIgG4 to Phl p 1 and 5 was observed in serum of Group A (p = .047 and p = .0039) and sIgA2 to Phl p in Group B (p = .032 and p = .0098) at 18 and 24 months, respectively. Both local and systemic blocking antibodies can inhibit allergen–IgE complexes binding to CD23 on B cells, and this correlated with level of allergen tolerated intra‐nasally in Group A (serum; ρ = −.47, p = .0006, nasal; ρ = −.38, p = .0294). Conclusions Grass pollen SCIT induced functional systemic blocking antibodies that correlate with the concentration of allergen tolerated following NAC, highlighting their potential as a biomarker of SCIT in LAR. This study investigates SCIT capacity to induce local and systemic blocking antibodies in patients with local allergic rhinitis. Grass pollen SCIT induces functional systemic blocking antibodies. Grass pollen SCIT is associated with induction of functional Phl p specific IgA1/2 and IgG4 which can inhibit IgE‐facilitated allergen binding to CD23 on B cells and correlate with reduced allergen tolerated dose.Abbreviations: Ig, immunoglobulin; IgE‐FAB, IgE‐facilitated allergen binding; SCIT, subcutaneous allergen immunotherapy.