D2.196 - Elucidating the Immunological Mechanisms of Pollen Immunotherapy in Treating Food Allergy in Patients with Pollen-Food Allergy Syndrome

This study aimed to elucidate the immunological mechanisms underlying the clinical improvement of pollen-food allergy syndrome (PFAS) observed in patients receiving Fagales (birch and oak) pollen immunotherapy. Specifically, we investigated whether immunotherapy-induced IgG4 and blocking antibodies against PR-10 pollen allergens exert cross-blocking effects on homologous PR-10 food allergens, thereby inhibiting IgE-mediated allergic responses.

Serum samples were obtained from 25 patients diagnosed with pollen-food allergy syndrome (PFAS), including 12 patients who had received Fagales pollen immunotherapy for more than one year and 13 untreated controls. PR-10 related Fagales and vegetable food allergens (Bet v 1, Que a 1, Mal d 1, Pru p 1, Ara h 8, and Pana g 1)-specific IgE (sIgE) and IgG4 (sIgG4) levels were quantified using ImmunoCAP, and their binding profiles were evaluated by immunoblotting. Functional IgE-blocking activity against PR-10 pollen and vegetable food allergens was assessed using an IgE blocking factor assay. In addition, sIgG4 avidity against these allergens was analyzed by acidic dissociation ELISA.

Allergen-sIgG4 responses were generally increased in patients receiving immunotherapy, with a significant elevation observed for Bet v 1 (p<0.05), whereas IgG4 levels to Pru p 1 (p=0.272) and Ara h 8 (p=0.449) were not significantly increased in the immunotherapy group. Immunoblot analysis demonstrated enhanced IgG4 binding to birch, oak, and PR-10–related food allergens in immunotherapy-treated patients. Acidic dissociation ELISA revealed that IgG4 antibodies from immunotherapy-treated patients maintained more stable binding under decreasing pH conditions. Functionally, sera from the immunotherapy group exhibited higher IgE-blocking activity against birch and oak pollen allergens, whereas little difference for PR-10 related vegetable food allergens.

Fagales pollen immunotherapy increases the concentration and affinity sIgG4 in addition to the blocking activity to Fagales pollens, whereas minimal changes were found to the related vegetable food allergens.