Natural Course and Prognostic Factors of Immediate-Type Peanut Allergy in Children

<b><i>Background:</i></b> Predicting food allergy resolution is essential to minimize the number of restricted foods in children. However, there have been no studies on the natural history of peanut allergy (PA) in Korea. <b><i>Objective:</i></b> This study aimed to evaluate the natural course and prognostic factors of immediate-type PA in children till the age of 10 years. <b><i>Methods:</i></b> We retrospectively collected data of 122 children who developed PA before 60 months of age from 3 tertiary hospitals in Korea. Diagnosis and resolution of PA was defined as an oral food challenge test or a convincing history of symptoms within 2 h after peanut ingestion. The prognostic factors for resolution of PA were identified using the Cox proportional hazard model. <b><i>Results:</i></b> The median (interquartile range) age at diagnosis was 2.0 (1.3–3.0) years. Among the 122 children, PA resolved in 18 (14.8%) children. The level of peanut-specific IgE (sIgE) at diagnosis in the persistence group was significantly higher than that in the resolution group (<i>p</i> = 0.026). The probabilities of resolution of PA were 10.3% and 32.8% at the ages of 6 and 10 years, respectively. A peanut-sIgE level ≥1 kU/L at diagnosis was significantly associated with persistent PA (hazard ratio, 5.99; 95% confidence interval, 1.89–18.87). <b><i>Conclusions:</i></b> Only 10.3% of our patients had a probability of developing spontaneous resolution of PA by 6 years of age. Peanut-sIgE levels ≥1 kU/L at diagnosis were associated with the persistence of PA.

The Diagnostic Importance of Recombinant Allergen IgE Testing in Patients with Hymenoptera Venom Allergy: Comparison of Two Methods

Adults with systemic anaphylactic reactions (SAR) to insect sting show often multiple-positivity of serum-specific IgE (sIgE) to Hymenoptera venoms. Unnecessary long-lasting venom-specific immunotherapies (VIT) in false-positive patients increase the risk of recurrent SAR. This report aims to analyze the diagnostic importance of recombinant allergen IgE testing in patients with SAR to Hymenoptera sting.In 82 patients we measured sIgE to honeybee venom (HBV), wasp venom (WV) and hornet venom (HV) extracts, recombinant phospholipase A2 from HBV (sIgE-rApi m1), recombinant antigen 5 from WV (sIgE-rVes v5), and cross-reactive carbohydrate determinants-CCD-bromelain by ImmunoCAP. We analyzed the correlation of ImmunoCAP and Immunoblot for HBV and WV extracts, rApi m1, and rVes v5 in 39/82 patients. According to the history of the culprit insect, we compared sensitivity and specificity between the two methods.The severity of the SAR does not depend on the sIgE level to venom extracts and recombinant allergens. Fifty-one percent of the patients had a multiple-positivity to HBV/WV or HBV/WV/HV extracts. Severe SAR and CCD-sIgE were more frequent in multiple-positive than single-positive patients. CCD-sIgE were more frequent in HBV allergic patients than WV and HV allergic patients. There was a significant correlation between levels of sIgE to venom extracts and recombinant allergens measured by ImmunoCAP and Immunoblot. ImmunoCAP has higher sensitivity and specificity than Immunoblot for diagnosis of SAR to Hymenoptera venoms.IgE testing to recombinant CCD-free allergens is necessary for the adequate selection of long-lasting VIT, especially in patients with multiple sensitivities to venom extracts.

Assessment of TSLP, IL 25 and IL 33 in patients with shrimp allergy

Background Shrimp allergy is a growing problem among the European population. TSLP, IL-25 and IL-33 are involved in the pathophysiology of allergic diseases, including asthma and atopic dermatitis, as they activate the Th2-dependent immune response. Methods Thirty-seven patients (18 male and 19 female) with a positive history of symptoms associated with shrimp consumption were selected. All patients had blood samples taken to assess the concentration of allergen-specific IgE (sIgE) to house dust mites (HDM) and shrimp (Singleplex, quantitative method with cut off value > 0,35 kAU/L) as well as the level of allergen components using the ImmunoCap ISAC method (Microarray test, semi-quantitative with cut off value > 0,3 ISU-E). The concentrations of TSLP, IL-25 and IL-33 in the patients’ blood serum was assessed using the ELISA method (Cusabio). Twenty patients with negative allergy history of allergic disease tests were included in the control group. Results Among the 37 shrimp-allergic patients, ImmunoCap ISAC was identified the presence of sIgE to the available shrimp allergen components in only 14 cases (37.8%). TSLP and IL25 levels were significantly higher in the study group. No statistically significant correlation was found between the concentration of analyzed alarmins and the concentration of sIgE level to shrimp or HDM between the study and control groups. No statistically significant correlation was found between poly-sensitization occurring in patients and levels of TSLP, IL-25 and IL-33 . Conclusion In shrimp-allergic patients, the concentrations of TSLP and IL-25 were significantly higher than in the control group (1.33 vs. 0.49 and 157 vs. 39.36, respectively). There was no correlation between the concentrations of TSLP, IL-25 and IL-33 and the concentration of sIgE in the patients or the number of allergen components that the patients were sensitized to. Trial registration: Bioethics Committee 147/2015, 11.03.2015.

Component resolved diagnostics in peanut sensitized children with and without a history of clinical reaction

Background: Serum Peanut-specific-IgE (PN-sIgE) and peanut-component-resolved-diagnostics (CRD) are often ordered simultaneously in the evaluation for peanut allergy. Results often guide the plans for peanut oral challenge. However, the clinical utility of CRD at different total PN-sIgE levels is unclear. A commonly used predefined CRD Ara h2 cutoff value in the literature predicting probability of peanut challenge outcomes is 0.35kUA/L. Objective: To examine the utility of CRD in patients with and without a history of clinical reactivity to peanut (PN). Methods: This was a retrospective chart review of 196 children with PN-sIgE and CRD testing, of which, 98 patients had a clinical history of an IgE-mediated reaction when exposed to PN and 98 did not. The Fisher's exact test was used to assess the relationship between CRD and PN-sIgE at different cutoff levels, McNemar test and Gwet’s approach (AC1 statistic) were used to examine agreement between CRD and PN-sIgE, and logistic regression was used to assess differences in the findings between patients with and without reaction history. Results: Ara h 1, 2, 3, or 9 (ARAH) levels ≤0.35 kUA/L were significantly associated with PN-sIgE levels <2 kUA/L rather than ≥2 kUA/L (p < 0.0001). When the ARAH threshold was increased to 1 kUA/L and 2 kUA/L, these thresholds were still significantly associated with PN-sIgE levels of <2, <5, and <14 kUA/L. These findings were not significantly different in patients with and without a history of clinical reactivity. Conclusion: ARAH values correlated with PN-sIgE. Regardless of clinical history, ARAH levels are unlikely to be below 0.35, 1, or 2 kUA/L if the PN-sIgE level is >2 kUA/L. Thus, if possible, practitioners should consider PN-sIgE rather than automatically ordering CRD with PN-sIgE every time. Laboratory procedures that allow automatically and reflexively adding CRD when the PN-sIgE level is ≤5 kUA/L can be helpful. However, further studies are needed in subjects with challenge-proven PN allergy.

High Dust Mite specific Immunoglobulin E (sIgE): a Promising Indicator of Allergic Rhinitis to Asthma

Background: House dust mites are the most prevalent allergens in patients with asthma and/or rhinitis in China. Cross-sectional data in 2009 have shown that allergic rhinitis often preceded or occurred at the same time as asthma in patients which was used to investigate the association of serum specific immunoglobulin E (sIgE) levels to house dust mite with the onset of asthma in patients with allergic rhinitis. Methods: 321 patients with allergic rhinitis were face-to-face interviewed and underwent sIgE tests to house dust mite. The temporal sequence of allergic rhinitis and asthma was documented. Univariate analysis, multinomial logistic regression, and Kaplan-Meier survival analysis were performed. Results: Of the 321 participants, 213 (66.4%) had asthma, which occurred after or simultaneously with rhinitis, and 108 (33.6%) suffered from allergic rhinitis only. After controlling basic parameters, factors correlated to sIgE, and essential factors considered by clinical allergists, the risk of developing asthma always increased with the levels of sIgE to house dust mite in all four models (p < 0.01). In Kaplan–Meier analysis, in the first ten years with allergy rhinitis, a high sIgE level represented a high probability of the coexistence of allergic rhinitis and asthma (p < 0.01). For house dust mite sIgE level 5-6, 5 years Rhinitis-Asthma Conversion Rate (RACR) had reached almost 70%. Conclusion: High-level house dust mite sIgE can exist as an indicator of rhinitis to asthma. It provides a theoretical basis for early intervention in patients with high sIgE levels in order to prevent asthma. This assessment and intervention should be performed at the early stage of rhinitis.

Component-Resolved Diagnostic Study of Egg Allergy in Northern Chinese Children

Background. Egg component-specific IgE can be useful to evaluate and diagnose egg allergy, but their prevalence and clinical significance remain unclear in the local population. Previous studies have led to contradictory results regarding the value of specific IgG and specific IgG4 in sensitization. Objective. We aimed to determine the level of specific IgE, IgG, and IgG4 antibodies to the major egg allergens in egg-allergic children. Methods. Children from 6 months to 10 years of age were recruited. Egg allergy was confirmed by either a strong clinical history or an increased egg white-sIgE level. Other allergies were diagnosed by reactivity to other allergens but without egg-related symptoms and history. The serum sIgE, sIgG, and sIgG4 levels to major egg allergenic components (Gal d 1, Gal d 2, Gal d 3, Gal d 4, and Gal d 5), sIgE level to egg white, and tIgE level were determined by light-initiated chemiluminescent assay (LICA), ELISA, or ImmunoCAP. Results. Egg-allergic children had significantly higher levels of sIgE, sIgG, and sIgG4 to egg components than nonallergic children. Gal d 2 was the predominant allergen, and Gal d 2 sIgE level correlated with the egg white-sIgE level. Ratios of sIgE/sIgG4 to egg components were highest before 1 year of age and dropped gradually in the first decade of life. Conclusion. Patterns of sIgE to egg components could distinguish different forms of egg allergy. Ratios of sIgE/sIgG4 could be useful in predicting tolerance in egg-sensitive subjects, but this needs further evaluation and investigation using more accurate models.

Molecular allergen sensitization of Aspergillus fumigatus in allergic bronchopulmonary aspergillosis in Guangzhou, Southern China

Background Few studies have assessed the sensitization of mycotic allergens and Aspergillus fumigatus molecular allergen. This study aimed to investigate the connection between A.fumigatus components and mycotic allergens between allergic bronchopulmonary aspergillosis (ABPA) patients and A. fumigatus (Af)-sensitized asthma. Methods Serum Penicillium chrysogenum , Cladosporium herbarum , Mucor racemosus , Candida albicans , Alternaria alternata , Helminthosporium halodes and A.fumigatus allergen components (Asp f 1, Asp f 2, Asp f 3, Asp f 4, and Asp f 6) sIgE level were measured via ImmunoCAP assay in 18 ABPA patients and 54 Af-sensitized asthma patients in Guangzhou city. Results 94.44% of ABPA patients and 87.04% of Af-sensitized asthma patients were co-sensitization to at least one another fungal allergen. The positivity rates of C. albicans ( P < 0.05) and A.alternata ( P < 0.05) were higher in ABPA than that in Af-sensitized asthma patients. The positive rates of Asp f 1 (88.89% vs 59.26%, P < 0.05), Asp f 2 (66.67% vs 33.33%, P < 0.05), Asp f 4 (61.11% vs 33.33%, P < 0.05), and Asp f 6 (66.67% vs 14.81%, P < 0.001) in ABPA were higher than those in Af-sensitized asthma patients. Patients with ABPA had higher IgE levels of Asp f 1 ( P < 0.05), Asp f 4 ( P < 0.05) and Asp f 6 ( P < 0.001) than those of Af-sensitized asthma patients. A.fumigatus was strongly correlated with C.herbarum ( r s = 0.688) in ABPA and A.alternata ( r s = 0.692) in Af-sensitized asthma patients. Optimal scale analysis was show that ABPA was more relevant to Af-components. (Cronbach`s alpha = 90.7%) Conclusion The A.fumigatus components and it`s connection with various mycotic allergens were different in ABPA and Af-sensitized asthma patients. This findings can expected to help local doctors in the diagnosis and immunotherapy of fungal allergies.

Expression Level of MiRNA-126 in Serum Exosomes of Allergic Asthma Patients and Lung Tissues of Asthmatic Mice

Background: To investigate MiRNA-126 amounts in serum exosomes from allergic asthma patients as well as lung tissues of asthmatic mice, evaluating the expression of its target gene DNMT1 in mouse specimens. Methods: MiRNA-126 amounts in serum exosomes from asthmatic patients were detected by real-time PCR. The mouse model of allergic asthma was established by OVA-sensitization, and allergic symptoms were recorded; serum IL-4 and sIgE level evaluation (ELISA), broncho alveolar lavage fluid (BALF) cell count and H&E staining were performed to assess airway inflammation. MiRNA-126 and DNMT1 levels in the lung of asthmatic and control mice were detected by real-time PCR; DNMT1 protein levels were detected by immunoblot. Results: MiRNA-126 amounts in peripheral blood exosomes from patients with allergic asthma were significantly higher than that of healthy volunteers (P<0.05). The frequencies of scratching of both sides of the nose and sneezing were elevated within 10 min of excitation in asthmatic rats compared with controls. Meanwhile, OVA-sIgE and IL-4 levels were significantly higher in asthmatic animals than controls (P<0.05). In the asthma group, narrowed bronchial lumen and thickened wall were observed, and bronchial and peripheral vessels showed overt inflammatory cell infiltration. Eosinophil, neutrophil and mast cell amounts in the BALF of asthmatic mice were significantly higher than control values. Furthermore, lung miRNA-126 expression in asthmatic mice was significantly higher than that of controls. Finally, DNMT1 mRNA and protein levels were significantly lower in asthmatic animals compared with controls (P < 0.01). Conclusion: MiRNA-126 is highly expressed in serum exosomes from allergic asthma patients and lung tissues of asthmatic mice, suggesting that it may be involved in the pathogenesis of bronchial asthma.

Responsiveness of Nasal Provocation Testing—But Not Skin Test and Specific Immunoglobulin E Blood Level—Correlates With Severity of Allergic Rhinitis in Dermatophagoides Species-Sensitized Patients

Background The results of skin and blood allergen testing are not consistently relevant to clinical manifestations in allergic patients. Objective The aim of the study was to investigate the relationship between severity of allergic rhinitis and different allergen diagnostic tests in Dermatophagoides species-sensitized patients. Methods Study subjects included 65 rhinitis patients—50 with Dermatophagoides pteronyssinus (DP) sensitization (DP+) and 15 without DP sensitization (DP−), and 15 DP+ and 37 DP− healthy controls (HCs) confirmed by allergen skin prick (SPT) and blood specific immunoglobulin E (sIgE) tests. The Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) was tested. All subjects underwent DP nasal provocation test (DP-NPT). Visual analogue scoring (VAS) of nasal symptoms and nasal airway resistance (NAR) were measured before and after NPT. Correlations between the 3 allergen tests and score of RQLQ were performed. Results All rhinitis subjects had significantly higher VAS and NAR after DP-NPT than HCs ( P < .01). All DP+ rhinitis, 40% of DP− rhinitis subjects, 13.3% of DP+ HCs and 0% of DP− HCs had positive DP-NPT. Dose of positive DP-NPT positively correlated with SPT diameter and sIgE level in all tested subjects ( P < .001). Score of RQLQ positively correlated with dose of DP-NPT ( P < .001), but not with SPT diameter and sIgE level in rhinitis patients. Conclusion Although DP nasal provocation, skin prick wheal size and blood sIgE level correlate with each other, only nasal provocation testing is associated with severity of nasal symptoms. It is suggested that NPT should be performed to verify a clinically relevant allergy.