Takayasu Nomura

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.

Food sensitization in Japanese infants is associated with a common Filaggrin variant

1 51 F 320 Y 35 20 9 1 10 5 4 2 0.43 0.29 2 78 M 300 N 37 21 13 5 12 11 4 4 2.29 0.14 3 67 M 560 Y 56 47 11 12 8 6 4 2 1.86 0.86 4 55 F 102 N 10 3 6 2 24 20 8 8 1.14 0.43 5 51 F 120 N 38 30 11 5 7 2 4 2 0.57 0.29 6 55 M 590 N 42 18 9 5 19 12 8 5 3.14 0.86 Mean (SD) 60 (11) e 332 (209) e 36 (15) 23 (15) 10 (2) 5 (4) 13.3 (6.7) 9.3 (6.4) 5.3 (2.1) 3.8 (2.4) 1.6 (1.1) 0.5 (0.3) P value e e e e .005 .017 .007 .030 .034

Effect of Japanese cedar specific immunotherapy on allergen-specific TH2 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.

Probability curves for predicting symptom severity during an oral food challenge with wheat

Wheat allergy is the third most common food allergy among young children in Japan.1 The most reliable examination for the definitive diagnosis of a food allergy is an oral food challenge (OFC); however, consuming wheat appears to be an independent risk factor for anaphylaxis during OFC.2 As predictive factors for severe wheat OFC outcomes have not yet been identified, simple and easy indicators to predict induced symptom severity during wheat OFCs are needed. Omega-5 gliadin is a major allergen in young children with an immediate allergic reaction to wheat,3 and the serum u-5 gliadin-specific IgE level was reported to be a useful parameter for predicting positive OFC outcomes.4,5 Conversely, we previously reported probability curves for predicting symptom severity during egg and milk OFCs based on allergen-specific IgE levels6,7 to add clinical usefulness to these that only predict positive outcomes.1 Here we report probability curves for predicting symptom severity during a wheat OFC. In this study, unified OFC protocols with a single database system were used to conduct a total of 1679 OFCs at 14 institutions between October 2012 and May 2014. The indication for OFC was decided according to the Japanese guidelines for food allergy with their clinical history of food allergy and related specific IgE levels.1,8 Of 173 wheat OFC cases, 117 OFCs with sufficient data for patients aged 6 years were included in the final analysis. We excluded 56 cases including 4 older patients, 16 cases of insufficient dosing, 3 inconclusive cases, and 33 cases without appropriate specific IgE data. Udon noodles were used for wheat exposure; children ingested 1, 2, 5, 10, and 20 (or 30) g of udon noodles in increasing order at intervals of 15e30 min. Considering that udon noodles contain 3.1% wheat protein,8 the maximal total consumed wheat proteins was 1488 mg during OFCs. An OFC was terminated once a distinct allergic symptom was induced following ingestion. Severity of induced allergic symptoms was graded from 1 to 5 using the grading system of the guideline,1 which is based on Sampsons anaphylaxis severity score.9 In this study, a negative outcome was defined as the consumption of at least 38 g of udon noodles without any induced symptoms.8 Serum u-5 gliadinand wheat-specific IgE levels were monitored for 3 months prior to OFCs using the ImmunoCap test (Thermo Fisher Scientific, Uppsala, Sweden). The present study was approved by a local research ethics committee. In statistical analyses, allergen-specific IgE levels, which were out of detection limits, were considered as 0.17 kUA/L for levels

Diffuse alveolar hemorrhage secondary to ANCA-associated vasculitis in a patient with Down syndrome

Diffuse alveolar hemorrhage (DAH) is a rare disease characterized by dyspnea, cough, hemoptysis, and new alveolar infiltrates. Among the various underlying disorders, vasculitis is believed to play a significant role in the pathogenesis of DAH. Here we report the first case of a patient with Down syndrome who developed DAH secondary to anti‐neutrophil cytoplasmic antibody‐associated vasculitis. This case highlights the significance of vasculitis as well as pulmonary hypoplasia and vulnerability associated with Down syndrome in the development of DAH.

Multicolor flow-cytometric analysis of milk allergen-specific T-helper type 2 cells revealed coexpression of interleukin-4 with Foxp3

BACKGROUND Allergen-specific T-helper type 2 (TH2) cells play an important role in the development of allergic inflammation; however, investigations of the properties of allergen-specific T cells have been challenging in humans. Despite clear evidence that forkhead box p3 (Foxp3) is expressed in conventional effector T cells, its function has remained unknown. OBJECTIVE To characterize allergen-specific TH2 cells in milk allergy, with particular focus on the expression of Foxp3. METHODS Twenty-one children with milk allergy and 11 children without milk allergy were studied. Peripheral blood mononuclear cells from subjects were stimulated with milk allergen for 6 hours and analyzed using multicolor flow cytometry to identify CD154(+) allergen-specific T-helper cells. Simultaneously, the expression of intracellular cytokines and Foxp3 was analyzed. RESULTS The milk allergy group had significantly larger numbers of milk allergen-specific interleukin (IL)-4- and IL-5-producing CD4(+) T cells than the control group. Subjects in the milk allergy group had significantly more CD154(+)CD4(+) IL-10-producing cells and CD154(+)Foxp3(+)CD4(+) cells than those in the control group. In addition, the number of milk allergen-specific CD154(+)Foxp3(+)CD4(+) cells strongly correlated with that of CD154(+)IL4(+)CD4(+) cells. Bcl-2 expression in CD154(+)IL-4(+)Foxp3(+) T-helper cells was significantly lower compared with that in total CD4 cells. CONCLUSION Increased numbers of IL-4-producing allergen-specific T-helper cells were found in patients with milk allergy. In addition, Foxp3 was coexpressed with IL-4 in allergen-specific TH2 cells from patients. This coexpression was associated with lower Bcl-2 levels and could contribute to the phenotype and function of TH2 cells.