Background:The effect of oral immunotherapy (OIT) on wheat allergy is promising in terms of the potential to obtain desensitization; however, the frequency of exerciseinduced allergic reactions on desensitization (EIARDs) and the associated risk factors remain to be determined. Methods:Twenty-five patients underwent rush OIT for wheat allergy, and 21 achieved the full-dose intake of wheat products (5 g of wheat protein). Exerciseprovocation tests were repeatedly performed after the ingestion of a full-dose wheat product. The time-course of the levels of the specific IgEs (sIgE) to wheat extract, total gliadin, deamidated gliadin, recombinant gliadin components (α/β-, γ-and ω-5-), and glutenin (high and low molecular weight) components was analyzed using ImmunoCAP ® , ELISA, or IgE immunoblotting.Results: Fourteen patients (66.7%) were diagnosed as EIARD+, which remained 5 years after rush OIT in 11 patients (52.4%). There were no differences in the clinical backgrounds of the EIARD+ and EIARD− patients. However, EIARD+ patients showed significantly higher sIgE levels to all gliadin and glutenin components than EIARD-patients before OIT. The sIgE levels to each component decreased equally after 1 and 2 years of OIT. On IgE immunoblotting, sera from all patients reacted to the multiple gluten bands, and some reacted to the water-soluble bands. The intensity of all IgE-reactive bands also became equally lighter after OIT. Conclusions:EIARDs were frequently observed and remained for a long period after successful OIT for wheat allergy. None of the specific wheat components were found to contribute to EIARDs. K E Y W O R D S allergen component, exercise-induced allergic reaction, exercise-provocation test, oral immunotherapy, wheat allergy | 1415 FURUTA eT Al.

Casein (CN) is the major cow's milk (CM) allergen in patients with CM allergy (CMA). 1 Bovine CN consists of four fractions, αs1-, αs2-, β-, and κ-CNs.Oral immunotherapy (OIT) is a recommended clinical procedure, 2 and its curative effect and induced changes in the immune response are promising. 3-5 Studies on CM-OIT have reported decrease in specific IgE (sIgE) and increase in specific IgG4 (sIgG4) levels to CM proteins, CN, or whey proteins. 6,7 However, only few studies have focused on CN component-specific antibodies during CM-OIT.

Casein (CN), a major allergen for patients with persistent cow's milk (CM) allergy, comprises approximately 80% of CM proteins. 1 Bovine CN is constituted of four components, αs1-, αs2-, β-, and κ-CN, and exists as a micelle with a 30-300 nm diameter. 2 CN is an unfolded phosphoprotein and interacts with calcium phosphate in milk. 3 αs-CN is defined as an insoluble fraction in 0.4 mol/L calcium chloride, while κ-CN is the soluble fraction. β-CN is defined as soluble in 3.3 mol/L urea and insoluble in 1.7 mol/L urea. Bovine αs1-, αs2- ,

Introduction: Immune response to cow's milk allergen (CMA) has been analyzed mostly using crude milk antigen or a mixture of various caseins. This study aimed to assess the changes in the immunological response against αS1-casein during oral immunotherapy (OIT) and to investigate the mechanism of tolerance. Methods: We have performed rush OIT to 39 patients with CMA and obtained the serum samples up to 3 years after OIT. Immunoglobulin E (IgE) and IgG4 antibodies specific to highly purified αS1-casein as well as passively-sensitized basophil activation were evaluated using the serial samples. Furthermore, we examined whether basophil activation led by the pre-OIT serum was suppressed by the post-OIT serum, or by the tolerant serum obtained from naturally outgrown patients. Results: Specific IgE to αS1-casein was significantly reduced after OIT. Specific IgG4 (sIgG4) to αS1-casein was also detected in most of the pre-OIT sera, which was not significantly increased after OIT. Activation of passivelysensitized basophils to αS1-casein was significantly reduced after 2 years (14% ± 19%) and 3 years (19% ± 18%) post-OIT compared with pre-OIT (%CD63 high basophils; 51% ± 27%). Furthermore, the addition of post-OIT or tolerant serum to pre-OIT serum significantly suppressed the basophil activation. This suppression was abrogated by washing the supernatant after passive sensitization, but not by depleting IgG antibodies from post-OIT or tolerant sera, nor by blocking FcγRIIb using an anti-FcγR antibody. Conclusions: αS1-casein-sIgG4 plays a minor role in tolerance mechanisms in cases of CMA; humoral factors other than antigen-sIgG4 may be involved.