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Background In the LIBERTY ASTHMA QUEST (ClinicalTrials.gov: NCT02414854 ) study, dupilumab 200 mg and 300 mg every 2 weeks vs matched-volume placebo reduced severe asthma exacerbations and improved lung function (FEV1), asthma control, and quality of life in patients with uncontrolled, moderate-to-severe asthma (N = 1902). Here, we examine the safety and efficacy of dupilumab in the subpopulation of Japanese patients who participated in QUEST (n = 114; 6%). Methods Endpoints assessed were annualized severe exacerbation rates and the effect of treatment over the 52-week treatment period on FEV1, asthma control, asthma-related quality of life, and markers of type 2 inflammation. Results In Japanese patients, dupilumab 200 and 300 mg every 2 weeks vs matched placebo reduced severe asthma exacerbation rates by 44% (P = 0.33) and 75% (P = 0.03), respectively, and improved FEV1 at Week 12 by 0.20 L (P = 0.05) and 0.17 L (P = 0.12). FEV1 improvements were rapid (by Week 2) and sustained throughout treatment. Significant and/or numerical improvements vs placebo in asthma control and quality of life were also observed throughout treatment. For each endpoint, greater efficacy was observed in patients with elevated baseline levels of type 2 inflammatory biomarkers (blood eosinophils or FeNO). Dupilumab treatment significantly reduced levels of FeNO and total IgE, but not blood eosinophils. Conclusions In this subanalysis of QUEST, the efficacy and safety of dupilumab in Japanese patients was comparable to that observed in the overall intention-to-treat population, suggesting no variability in efficacy on the basis of Japanese ethnicity. (Funded by Sanofi and Regeneron Pharmaceuticals, Inc.; ClinicalTrials.gov number: NCT02414854 )

Background: Omalizumab is effective and well-tolerated in children with moderate to severe allergic asthma. However, the effects of long-term treatment with omalizumab in this population haven't been well investigated. The objective of this study is to evaluate the long-term safety, efficacy, pharmacokinetics and pharmacodynamics of omalizumab in children with uncontrolled severe asthma. Methods: Thirty-eight Japanese children (aged 7–16 years) who completed the 24-week treatment core study were included in an uncontrolled extension study, in which treatment with omalizumab continued until the pediatric indication was approved in Japan (ClinicalTrials.gov number: NCT01328886). Results: Thirty-five patients (92.1%) completed the extension study. The median exposure throughout the core and extension studies was 116.6 weeks (range, 46.9–151.1 weeks). The most common adverse events were nasopharyngitis, influenza, upper respiratory tract infection, and asthma. Serious adverse events developed in 10 patients (26.3%), but resolved completely with additional treatments. Incidence of adverse events didn't increase with extended exposure with omalizumab. Twenty-nine patients (76.3%) achieved completely- or well-controlled asthma compared with 9 patients (23.7%) at the start of the extension study. QOL scores, the rates (per year) of hospitalizations and ER visits were significantly improved compared with the baseline of the core study [39.0 vs 48.0 (median), p

Background: Omalizumab, a monoclonal anti-IgE antibody, is currently indicated for the treatment of moderate-to-severe allergic asthma. To measure active IgE levels in sera from patients treated with omalizumab, the IgE subfraction in complex with omalizumab should be eliminated from total IgE, and free IgE levels can then be determined. With the aim of therapeutic monitoring for anti-IgE therapy, we developed a new ELISA for free IgE. Methods: We used recombinant human soluble FcεRIα as a capture antigen and a biotinylated polyclonal anti-IgE antibody for detection. Using the newly developed ELISA, we measured the serum free IgE levels weekly in four asthmatic patients after their first omalizumab injection. We also measured the serum free IgE levels in 54 patients treated with omalizumab for over 4 weeks. Results: This assay was technically robust, the mean recovery rate in serum was 93.16% ± 5.34%. For all patients, omalizumab treatment significantly reduced serum free IgE levels prior to the second omalizumab injection. To maintain the benefit of omalizumab, serum free IgE concentrations should be 50 ng/ml. Conclusions: Our data suggest that the measurement of free IgE levels using our newly developed ELISA would be useful for monitoring serum free IgE levels during omalizumab therapy.

Background: Screening patients for latex allergy prior to surgery is an important but intensive procedure. The appropriate testing strategy for diagnosing latex (Hevea brasiliensis) allergy involves in-vitro specific IgE or skin prick testing. The sensitivity and specificity of both tests are influenced by patient-specific factors or manufacturing processes that alter the clinically relevant allergens in skin testing solutions. Methods: Total IgE and latex-specific IgE testing was introduced as a screening test. Skin prick testing was done on patients with a high probability of latex allergy and negative specific IgE with total IgE

Background In studies on allergies in mouse models, IgE production is an essential parameter to be evaluated. Here, we examine the effect of commercially available immunoreaction enhancer solutions and different blocking reagents in enzyme-linked immunosorbent assay (ELISA) for total or antigen-specific murine IgE in order to improve the assays. Methods Sera from mice immunized with recombinant house dust mite major allergens, Der f 1 and Der p 1, were used for the assays. Total IgE was measured by sandwich ELISA using monoclonal antibodies against murine IgE. Antigen-specific IgE was assayed using allergen-coated plates. Sensitivity or signal intensity in ELISA was compared among conditions differing in the use of enhancer solutions, blocking reagents, or monoclonal antibodies, and incubation time. Results Use of enhancer solutions improved the sensitivity of ELISA for total IgE by approximately 30-fold of that using a conventional buffer. A blocking reagent caused more unwanted enhancement of the background signal in blank wells in ELISA for total IgE compared with another blocking reagent, however, improved signal intensity in ELISA for antigen-specific ELISA without significant enhancement of the background signal. Optimal assay conditions were determined. Conclusions Enhancer solutions are effective in improving ELISAs for total and antigen-specific murine IgE. Selection of blocking reagents was important to decrease unwanted enhancement of background signals and was effective in enhancing signals for positive samples. The ELISAs improved in this study are useful for the study of allergies in mouse models.

Background The development of an inexpensive point-of-care testing system for antigen-specific IgE is greatly needed. We, therefore, tried to develop a quantitative enzyme immunochromatography assay system for antigen-specific IgE in fresh whole blood. Methods Whole blood sample was mixed with a reagent containing detergent to lyse red blood cells, and the mixture was applied to an immunochromatography strip. The lysate was observed to migrate in the strip and was washed away by the substrate buffer. When the sample contained the specific IgE, the antigen-specific IgE line was clearly observed on the strip macroscopically. Results Results were obtained 20 minutes after the application of hemolysed blood sample to immunochromatography, and these results showed positive correlation with those obtained by the AlaSTAT system, which is one of the popular assay kits for specific IgE. The results were not affected significantly by the hematocrit value of the blood sample, by the kind of anticoagulant in the blood collection tube, or by the concentration of the total IgE, provided it was lower than 20000 IU/ml. Conclusions These results indicate that our system is applicable for point-of-care testing for antigen-specific IgE.

Background Background data on the allergic constitutions of a general population of Japanese children may provide important information regarding environmental factors that contribute to the increased incidence of allergic diseases and suggest clues for their prevention. Methods Serum samples were obtained from a general population of 3-year-old children (612 samples) in the Kanto area and Asahikawa city. The serum levels of total and specific IgE antibodies against food allergens (egg white, milk, soybean, wheat), indoor airborne allergens (house dust, mite, cat dandruff), and outdoor airborne allergens (Japanese cedar or white birch pollen allergens) were determined and analyzed, along with the results of a questionnaire regarding medical history, and allergy-related subjective symptoms. Results The mean total IgE level of all subjects was 34.7 IU/ml, while that for the Kanto and Asahikawa areas was 44.7 and 22.5 IU/ml, respectively. Twenty six percent of the 612 children were judged positive for indoor airborne allergen-specific IgE, and 6.7% were positive for food allergen-specific IgE. Cedar allergen-specific IgE was detected in 15.6% of the children living in the Kanto area. The total IgE level was strongly correlated with the number of allergens to which the child was sensitized. Conclusions A relatively large number (28.4%) of 3-year-old children possessed allergen-specific IgE antibodies. The basic data obtained in the general population in these two areas of Japan will be valuable for further evaluations of environmental influences on allergic disease.

BackgroundTotal serum IgE may be increased in alcoholics. IgE synthesis depends on B cell activation by Th2-type cytokines. Serum sCD30 has been proposed as a marker of Th2 responses. The aim of the present study was to evaluate serum sCD30 levels in alcoholics and their relationship with serum IgE values.MethodsTwenty-five active alcoholics and 18 healthy controls were included in the study. All subjects were non-atopic (asymptomatic from the allergologic point of view and Phadiatop® (Phamacia & Upjohn Diagnostics AB, Uppsala, Sweden) negative). Serum IgE was measured by chemiluminescent enzyme immunoassay and serum sCD30 was assayed by ELISA.ResultsTotal serum IgE was higher in alcoholics than in controls (median (range) for alcoholics and controls 59 (15.8-236) vs 24 (4-103) IU/mL, respectively; P = 0.003). Conversely, median serum sCD30 levels were lower in alcoholics than in controls (

A new method is described for the quantitative detection of IgE antibodies, based on IgE capture with a specific antibody, reaction with liquid-biotinylated allergens and biotinylated anti-IgE and immunoenzymatic development of the reaction (reverse enzyme allergosorbent test). Using a reference system based on the World Health Organization IgE International standard, this method determines total IgE in the range 2-100kU/L and specific IgE in the range 0.2-100 kU/L, from which the specific/total ratio, called 'specific IgE density', can be calculated. This procedure has been applied to the study of specific IgE in 23 sera from patients polysensitized to pollen and mite allergens: 11 with asthma and 12 with rhinitis. The sensitivity and reproducibility of the method were evaluted. Sera from asthmatic patients showed higher cumulative levels of specific IgE (mean density 57.7%) than sera from rhinitic patients (mean density 32.6%). The clinical significance of specific IgE density in patients with multiple sensitizations is discussed.

We examined the IgE and IgG antibody responses in Japanese cedar pollinosis patients before and after the pollination season for 2 years. The sera from 90 patients in 1990 and 87 in 1991, living in five regions in the Tokyo area, were obtained before and after the pollination season. In all patients, changes (increase then decrease) in specific IgE levels were detected after natural pollen exposure. Total IgE and specific IgG concentrations also changed. However, the degree of change in specific IgE was greater than those in total IgE and specific IgG. Then, the geometric means of specific and total IgE levels were compared among the five regions. These levels were found to be highest in the region where the pollen count was the highest. These findings suggest that IgE antibody production is more stimulated after natural pollen exposure compared to IgG antibody production, and is dependent on the amount of allergens.

Background Because microflora has been reported to have an important effect on the development of allergic disorders, we measured intestinal microflora levels in 4-month-old infants and studied the development of allergic disorders. Methods Blood samples from 18 4-month-old infants and 15 1-year-old infants were examined for total serum IgE and specific IgE antibodies. Stool samples from 18 4-month-old infants were examined for the presence of microflora. Results A positive correlation was observed between the ratio of breast-feeding at 1 month and the percentage of bifidobacteria in the intestine at 4 months (correlation ratio=0.54; P = 0.022). Atopic dermatitis was observed in 12 of 18 infants at 4 months and in five of 15 infants at 1 year. Egg white-specific IgE was positive (≥0.70 U A /mL) in six infants at 4 months and in seven infants at 1 year. No relationship was observed between the percentage of bifidobacteria, lactobacilli or clostridia in the intestinal tract at 4 months and the development of allergy. However, all five infants who exhibited a percentage of bacter- oides (compared with the total intestinal microflora level) of more than 10% at 4 months had positive egg white-specific IgE and higher levels of total IgE (>25 IU/mL) at 1 year; these relationships were statistically significant ( P = 0.01). Conclusions Colonization with bacteroides at 4 months of age is suggested to be related to the allergic state at 1 year of age.

To estimate the levels of serum IgE that is actually able to be bound to FceRI, we developed a novel enzyme-linked immunosorbent assay (ELISA) using a recombinant soluble form of the human FceRIα ectodomain (soluble α-ELISA). We evaluated the levels of FceRI-bindable serum IgE in normal volunteers and in patients with atopic dermatitis and bronchial asthma, and compared them with those of total IgE measured by a conventional sandwich-ELISA. There was a striking difference between the IgE values evaluated with these two ELISA systems. In most of the sera, the IgE values evaluated with the soluble α-ELISA were substantially lower than those evaluated with the sandwich-ELISA. Our results indicate that all serum IgE (especially in hyper-lgE sera) does not necessarily bind to the FceRI and that it will be useful to evaluate FceRI-bindable IgE for further analysis of allergic states.