Diagnostic Decision Point for IgE-Mediated Wheat Allergy in Children.

The diagnostic decision point can help diagnose food allergies while reducing the need for oral food challenge (OFC) tests. We performed a multicenter survey of children aged 0-7 years from January 1, 2018 to March 31, 2022. A total of 231 children were recruited from 18 institutions. Wheat allergy (WA) or non-wheat allergy (NWA) was determined on the basis of OFC results and symptoms. There were no differences in age, sex, family history of allergy or allergic comorbidities between the WA and NWA groups. According to receiver operating characteristic analysis for wheat-specific immunoglobulin E (IgE), the optimal cutoff value, positive decision point, and negative decision point were 10.2, 33.5, and 0.41 kU/L, respectively. For the ω-5 gliadin-specific IgE, their values were 0.69, 3.88, and 0.01 kU/L, respectively. This new diagnostic decision point may be used to diagnose WA in Korean children.

Clinical utility analysis of the Hoxb8 mast cell activation test for the diagnosis of peanut allergy.

BACKGROUND: Peanut allergy is among the most severe and common food allergies. The diagnosis has a significant impact on the quality of life for patients and their families. An effective management approach depends on accurate, safe, and easily implementable diagnostic methods. We previously developed a cell-based assay using Hoxb8 mast cells (Hoxb8 MCs) aimed at improving clinical allergy diagnosis. In this study, we assessed its diagnostic performance by measuring blinded sera from a prospectively enrolled and pre-validated peanut allergy cohort. METHODS: Hoxb8 MCs were passively sensitized with sera from peanut-allergic and peanut tolerant children and adolescents (n = 112). Degranulation of Hoxb8 MCs was quantified upon stimulation with dose-titrated peanut extract by means of flow cytometry, using CD107a as activation marker. The results from the Hoxb8 mast cell activation test (Hoxb8 MAT) were compared to established diagnostic assays such as the skin prick test (SPT), specific IgE (sIgE) levels, and the basophil activation test (BAT). Additionally, serum samples from BAT nonresponders were assessed with the Hoxb8 MAT. RESULTS: Hoxb8 MAT displayed a robust dose-dependent activation to peanut extract, with a cutoff value of ≤5.2% CD107a positive cells. The diagnostic accuracy was highest at allergen concentrations ≥100 ng/mL, with an area under the receiver operating characteristic curve (AUROC) of 0.97, 93% sensitivity, and 96% specificity, outperforming traditional SPT and sIgE tests. When compared to BAT, Hoxb8 MAT exhibited comparable diagnostic efficacy. Moreover, sera from BAT nonresponders were accurately classified into allergics and nonallergics by the Hoxb8 MAT. CONCLUSIONS: The Hoxb8 MAT demonstrated a very good diagnostic precision in patients prospectively assessed for peanut allergy comparable to the fresh whole blood-based BAT. Additionally, it demonstrated its value for accurate classification of BAT nonresponders into allergic and nonallergic individuals. Further investigations into its utility in the routine clinical setting are warranted.

Evaluation of a Novel Detection Method for Allergen-Specific IgE Antibodies with IgE Receptor Crosslinking Using Rat Food Allergy Model.

The specific detection of serum IgE antibodies specific to allergens (sIgE Abs) that can crosslink the plural high-affinity IgE receptor (FcεRIα) molecules on the surface of mast cells or basophils with a multivalent allergen can reduce the false-positive diagnoses observed in chemiluminescent and fluorescence enzyme immunoassays for type-I allergic patients. In this study, we detected sIgE Abs to the egg-allergen ovalbumin (OVA) and the wheat-allergen gluten in the sera of rats sensitized with each allergen using an amplified luminescence proximity homogeneous assay by crosslinking (AlphaCL). OVA and gluten were reacted with each sIgE Ab in the sera. Then, acceptor and donor beads labeled with the human FcεRIα were added to the reacted solution. The luminescence intensity for anti-OVA IgE Abs in the sera with the removal of IgG Abs was observed in five of seven (71.4%) of the sensitized rats, whereas no signals were observed in any of the unsensitized rats. The AlphaCL could also detect anti-gluten sIgE Abs in the sera of sensitized rats, but not of unsensitized rats. In conclusion, we successfully detected sIgE Abs in the sera of rats sensitized to two allergens using the AlphaCL. This detection method has the potential to be used as a new diagnostic tool for type-I allergic patients.

[LONGITUDINAL EVALUATION OF EFFICACY OF SUBLINGUAL IMMUNOTHERAPY IN PEDIATRIC PERENNIAL ALLERGIC RHINITIS USING LABORATORY EXAMINATIONS AND IN VIVO BIOMARKERS].

OBJECTIVE: The purpose of this study was to evaluate the efficacy of sublingual immunotherapy (SLIT) with house dust mite (HDM) on pediatric perennial allergic rhinitis (AR) based on longitudinal assessment of nasal symptoms, laboratory examination, and in vivo biomarkers. METHOD: The subjects included 40 children with perennial AR who had SLIT with HDM for 2 years. Nasal symptoms, medications, skin prick tests, nasal provocation tests, and peripheral blood tests were evaluated before, 6 months, one year and two years after the onset of SLIT. RESULTS: Total nasal symptom scores, prick test wheal diameter, and peripheral blood eosinophil count decreased in 6 months. Total nasal symptom scores continued to decrease from 6 months to 2 years. Symptom-medication scores and nasal provocation test responses decreased in 1 year. Symptom-medication scores continued to decline from 1 to 2 years. Medication scores and nasal eosinophilia decreased in 2 years. Serum specific IgE to HDM slightly increased transiently and decreased in 2 years. The severity of symptoms and specific IgE to HDM at the baseline, and changes of symptoms and specific IgE to HDM during the first six months and first one year of SLIT were correlated with improvement in symptom scores over two years of SLUT. TNSS at baseline was correlated with that at second year. CONCLUSION: Longitudinal assessment of symptoms, allergen specific IgE, and in vivo biomarkers showed the effectiveness of SLIT. Symptom scores and allergen specific IgE may also be early predictive factors of SLIT efficacy in children with AR.

Fish and shellfish allergy: Presentation and management differences in the UK and US-analysis of 945 patients.

Background: Seafood allergy (SA), including allergy to shellfish (crustacean and mollusks) and fish, is among the 4 most common food allergies causing anaphylaxis, but there are limited data showing SA clinical management in different countries. Objective: We sought to characterize a large cohort of patients with fish and shellfish allergy and to facilitate standardization of future care for this increasingly common allergic disease. Methods: We performed a retrospective, observational, noninterventional study from 945 patients from 2015 to 2019 in 7 hospitals in the United States and the United Kingdom to evaluate SA. A chi-square test was used to detect differences in family history, medical history, and current symptoms between patients in 2 countries. Results: Underdiagnosed anaphylaxis in patients with SA was associated with underuse of epinephrine (adrenaline) autoinjectors in both countries. Oral food challenge was used only when skin or serologic test results were negative. Asthma and allergic rhinitis were more common in the US patients with SA, but eczema was more common in UK patients with SA (P < .001). Respiratory, gastrointestinal, and neurological symptoms were higher in UK patients with SA than in US patients with SA (P < .001). Conclusions: In international multicenter cohorts of patients with fish and shellfish allergy, there are opportunities for improvement in management. Physician identification of anaphylaxis, use of diagnostic oral food challenges, and anaphylaxis treatment with epinephrine are areas with significant knowledge gaps in need of improvement in the United Kingdom and the United States. There is an opportunity for the development of unified, standardized diagnostic protocols for SA with distribution for allergists and trainees.

Association between frozen embryo transfer and childhood allergy: a retrospective cohort study.

RESEARCH QUESTION: Does frozen embryo transfer (FET) increase the risk of allergic diseases in offspring? DESIGN: This study followed up 653 singleton children: 166 born through FET and 487 born through natural conception. Demographic characteristics, perinatal information and allergic diseases of children and their parents were collected through clinical medical systems and questionnaires. Among these 653 children, allergen-specific immunoglobulin E (IgE) testing was performed using peripheral blood samples collected from 207 children: 145 in the FET group and 62 in the natural conception group. The prevalence of allergic diseases and positive rates of allergen-specific IgE testing were compared between the two groups with adjustments for confounding factors. RESULTS: The prevalence of food allergy was significantly higher in children born through FET compared with children born through natural conception (adjusted OR = 3.154, 95% CI 1.895-5.250; P < 0.001). In addition, positive rates of food allergen sensitization were higher in children in the FET group compared with children in the natural conception group (adjusted OR = 5.769, 95% CI 2.859-11.751, P < 0.001). Children in the FET group had a higher positive sensitization rate to at least one allergen compared with children in the natural conception group (adjusted OR = 3.127, 95% CI 1.640-5.961, P < 0.001). No association was observed between FET and other allergic diseases, including asthma (P = 0.136), atopic dermatitis (P = 0.130) and allergic rhinitis (P = 0.922). Allergen sensitization IgE testing indicated no differences between the two groups in terms of positive sensitization rates of other common allergens, including animal and insect allergens (P = 0.627), inhaled outdoor allergens (P = 0.915) and inhaled outdoor allergens (P = 0.544). CONCLUSION: This study suggests that children born through FET have increased risk of developing food allergy in early childhood.

Allergic bronchopulmonary mycosis in Schizophyllum commune with positive Aspergillus-specific IgE antibodies: A case report.

Schizophyllum commune is the third most common causative fungus of allergic bronchopulmonary mycosis(ABPM). Two-thirds of ABPM caused by S. commune can be positive for Aspergillus fumigatus-specific IgE, which can be difficult to diagnose. Our patient presented to our hospital with wet cough for 3 months and chest pain for 3 days. Blood tests showed IgE 1522 IU/mL, eosinophils 688/mm3, A. fumigatus -specific IgE 2.24 UA/mL, and chest computed tomography showed high-attenuation mucus. Bronchoscopy showed mucus plugs and speculum examination showed filamentous fungi, but various culture tests did not detect A. fumigatus, Asp f 1-specific IgE was negative, and S. commune was detected in the culture of bronchial washing. Since he was positive for S. commune-specific IgE and IgG, he diagnosed ABPM caused by S. commune. These findings demonstrate the importance of identifying the causative fungus in ABPM by detailed examination.

Pru p 3-specific IgE affinity is crucial in severe peach-allergy patients.

Background: Peach allergy is common food allergen. Allergen components-specific antibodies of different isotypes in peach-allergy patients are poorly studied. Factors other than Pru p 3-sIgE levels may be related to severe symptoms. Objective: To evaluated peach component-specific-IgE, IgG1, and IgG4 characteristics in individuals with and without peach allergy, and Pru p 3-sIgE affinity in patients with different clinical symptoms. Methods: Fifteen healthy controls and 32 peach-allergy patients were enrolled. sIgE, sIgG1, and sIgG4 to 5 Escherichia coli-expressed peach-allergen components were determined by enzyme-linked immunosorbent assays. Pru p 3-sIgE affinity was measured in Pru p 3-sIgE-positive patients, using immunoadsorbance. Results: Patients were divided into oral allergy syndrome (OAS) and peach-induced anaphylaxis (PIA) groups. Serum Pru p 1-, Pru p 2-, Pru p 3-, Pru p 4-, and Pru p 7-sIgG1s were detected. Pru p 1- and Pru p 2-sIgG1 levels were higher in healthy controls, but Pru p 3-sIgG1 levels were significantly higher in peach-allergy patients. Pru p 1-, Pru p 3-, and Pru p 4-sIgG4-positivity was significantly greater among patients than among controls. Pru p 3 was the predominant allergen in peach-allergy patients. Allergen-sIgG1 and sIgG4 were similar between OAS and PIA patients. Pru p 3-sIgE levels were significantly higher in PIA patients, but Pru p 3-sIgE-positivity was similar in both groups. In Pru p 3-sIgE-positive patients, Pru p 3-sIgE affinity was significantly higher in PIA than OAS patients. Conclusions: Allergen-sIgG1 was associated with allergen exposure. Both Pru p 3-sIgE levels and affinity are key factors in severe peach-allergy patients.

Clinical and serological characteristics of patients allergic to LTP.

BACKGROUND: Allergy to lipid transfer proteins (LPT) is common in Mediterranean Europe, and it causes severe reactions in patients and affects multiple foods, impairing the quality of life. OBJECTIVE: This study aimed to describe the clinical and sensitization profile of patients with LTP syndrome and to determine a clinical pattern of severity. Molecular diagnosis is shown in a broad population through microarrays. MATERIAL AND METHODS: This study was performed at the LTP Allergy Consultation of the Reina Sofia Hospital in Murcia, Spain. We analyzed the patients' characteristics, reactions, cofactors, food implicated, quality of life, skin prick test to food and aeroallergens, and serologic parameters, such as total immunoglobulin E, peach LTP (Pru p 3 IgE) and immunoglobulin G4, and microarray Immuno Solid-phase Allergen Chip (ISAC). We related the severity of the reactions with other variables. RESULTS: We presented a series of 236 patients diagnosed with LTP allergy, 54.66% suffering from anaphylaxis, 36.02% from urticaria angioedema, and 9.32% from oral allergy syndrome. The most frequently implicated food was peach, producing symptoms in 70% of patients, followed by walnut in 55%, peanut in 45%, hazelnut in 44%, and apple in 38% patients. Regarding the food that provoked anaphylaxis, walnut was the most frequent instigator, along with peach, peanut, hazelnut, almond, sunflower seed, and apple. According to the severity of LPT reaction, we did not discover significant differences in gender, age, food group involved, and serologic parameters. We found differences in the presence of cofactors, with 48.84% of cofactors in patients with anaphylaxis, compared to 27.1% in patients without anaphylaxis and in family allergy background (P < 0.0001). CONCLUSION: In our series of patients, 54% presented anaphylaxis, and the foods that most frequently produced symptoms were peaches, apples, and nuts. Cofactors and family allergy backgrounds were associated with the severity of LPT reaction.