Decreased Basophil Activation against House Dust Mite after Japanese Cedar Pollen Subcutaneous Immunotherapy: A Retrospective Study.

BACKGROUND: Allergen-specific immunotherapy (AIT), an established treatment for allergic diseases, prevents the development of other allergic manifestations. Although the mechanisms remain unclear, AIT has been shown to reduce basophil activation (BA) against nontarget allergens. OBJECTIVES: The aim of this study was to assess immunological changes in Dermatophagoides farinae (Der f) after Japanese cedar pollen (JCP)-based subcutaneous immunotherapy (SCIT) monotherapy. METHOD: The data of 16 patients (age: 6-37 years) with JCP-induced allergic rhinitis who were sensitive to Der f (serum Der f-specific immunoglobulin E [IgE] level >0.34 kUA/L) and received JCP-based SCIT for 5 years were reviewed retrospectively. BA by Der f and JCP extracts and serum-specific IgE and immunoglobulin G4 (IgG4) levels against these allergens were evaluated before and after completing 5 years of JCP-based SCIT monotherapy. RESULTS: The areas under the dose-response curves of BA by Der f and JCP extracts were significantly reduced (p = 0.02 and p = 0.002, respectively). JCP-specific IgE levels decreased and JCP-specific IgG4 levels increased significantly (p < 0.001 for both), whereas Der f-specific IgE and IgG4 levels did not change significantly. CONCLUSIONS: JCP-based SCIT monotherapy reduced Der f-specific BA. These findings suggest that JCP-based SCIT has the potential to modulate immune response toward nontarget allergens.

Japanese cedar pollen-based subcutaneous immunotherapy decreases tomato fruit-specific basophil activation.

BACKGROUND: Some patients with Japanese cedar pollen (JCP)-induced allergic rhinitis develop pollen-food allergy syndrome (PFAS) as a reaction to tomato fruit. Pollen allergen-specific subcutaneous immunotherapy (SCIT) is reportedly beneficial for some associated food allergies; however, the reported changes in food allergen-specific immunoglobulin (Ig)E and IgG4 levels are inconsistent. Here, we investigated immunologic reactivity to tomato fruit after JCP-based SCIT. METHODS: Twenty-three children (aged 6-17 years) with JCP-induced allergic rhinitis and sensitized to tomato (serum tomato fruit-specific IgE level >0.34 UA/ml) received JCP-based SCIT. Basophil activation by tomato and JCP extracts and serum-specific IgE and IgG4 levels against these allergens were determined before and after 4 or 5 months of maintenance SCIT. Basophil activation was assessed by monitoring CD203c upregulation on flow cytometry. RESULTS: JCP-based SCIT significantly reduced the basophil activation caused by tomato fruit (p = 0.03) and JCP (p < 0.001) extracts. JCP-specific IgG4 levels markedly increased after SCIT (p < 0.001), whereas tomato fruit-specific IgG4 levels did not. After SCIT, no significant changes were observed in specific IgE levels for tomato fruit (p = 0.11) or JCP (p = 0.19). CONCLUSIONS: Tomato fruit-specific basophil activation decreases after JCP-based SCIT, suggesting that it is efficacious in relieving and preventing the symptoms of PFAS in patients with JCP-induced allergic rhinitis.

Effect of Japanese cedar specific immunotherapy on allergen-specific T(H)2 cells in peripheral blood.

BACKGROUND: The involvement of a shift from TH2 to TH1 responses in peripheral blood in pollen subcutaneous immunotherapy (SCIT) has been contentious, partly because of difficulties analyzing antigen-specific TH cells. OBJECTIVES: To use recent technical advances to establish a more direct and simple method to analyze antigen-specific TH cells and to clarify the involvement of a TH2/TH1 shift in peripheral blood in pollen specific immunotherapy. METHODS: After short-term (6-hour) antigen stimulation, antigen-specific TH cells in peripheral blood of Japanese children and young adults with Japanese cedar pollinosis undergoing SCIT were analyzed by multicolor flow cytometry for the presence of the activation marker CD154 and intracellular cytokines. RESULTS: Twenty-eight patients between 5 and 22 years of age were enrolled in the study; 22 had started SCIT after enrolling in the study (SCIT group), and the remaining 6 were planning to start SCIT in the next off-season (control group). The number of Japanese cedar-specific interleukin (IL) 5-, IL-4-, interferon γ-, IL-17A-, IL-10-, and tumor necrosis factor α-producing TH cells without antigen-driven cell proliferation was determined. The seasonal increase in the number of Japanese cedar-specific IL-5- and IL-4-producing TH cells seen in the control group was suppressed in the SCIT group (P < .005 and <.001, respectively). CONCLUSION: We report a powerful method for the analysis of antigen-specific TH cells in peripheral blood. This method will contribute to our understanding of immune mechanisms of immunotherapy and help us develop more sophisticated allergen specific immunotherapy.