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 (IgG(4), IgA(1) and IgA(2)) 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 sIgA(1) 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 sIgG(4) to Phl p 1 and 5 was observed in serum of Group A ( p =.047 and p =.0039) and sIgA(2) 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; rho = -.47, p =.0006, nasal; rho = -.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.