Background Component-resolved diagnosis might improve the prediction of future allergy in young children. Objective We sought to investigate the association between IgE reactivity to the ...pathogenesis-related class 10 (PR-10) protein family and allergic rhinitis to birch pollen (ARbp ) from early childhood up to age 16 years. Method Questionnaire data and sera obtained at 4, 8, and 16 years of age from the Barn/Children Allergi/Allergy Milieu Stockholm Epidemiologic (BAMSE) study birth cohort were used. Sera from 764 children were analyzed for IgE reactivity to 9 PR-10 allergen proteins at the 3 time points by using an allergen chip based on ISAC technology. ARbp was defined as upper airway symptoms during birch pollen exposure. Results IgE reactivity to Bet v 1 was found in 12%, 17%, and 25% of children at 4, 8, and 16 years of age. IgE reactivity of PR-10 proteins showed a hierarchic intrarelationship: Bet v 1 > Mal d 1 > Cor a 1.04 > Ara h 8 > Pru p 1 > Aln g 1 > Api g 1 > Act d 8 > Gly m 4. There was an increased risk of incidence and persistence of ARbp up to age 16 years with increasing levels of Bet v 1–specific IgE or increasing numbers of IgE-reactive PR-10 proteins at 4 years. Children with severe ARbp at age 16 years had higher levels of Bet v 1–specific IgE at age 4 years compared with children with mild symptoms. Conclusion ARbp at age 16 years can be predicted by analysis of IgE reactivity to PR-10 proteins in early childhood.
Background The nature of allergens and route and dose of exposure may affect the natural development of IgE and IgG responses. Objective We sought to investigate the natural IgE and IgG responses ...toward a large panel of respiratory and food allergens in subjects exposed to different respiratory allergen loads. Methods A cross-sectional analysis was conducted in 340 adults of the EGEA (Epidemiological study of the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy) (170 with and 170 without asthma) cohort. IgE and IgG responses to 47 inhalant and food allergen components were analyzed in sera using allergen microarray and compared between 5 French regions according to the route of allergen exposure (inhaled vs food allergens). Results Overall 48.8% of the population had allergen-specific IgE levels of 0.3 ISAC standardized units (ISU) or more to at least 1 of the 47 allergens with no significant differences across the regions. For ubiquitous respiratory allergens (ie, grass, olive/ash pollen, house dust mites), specific IgE did not show marked differences between regions and specific IgG (≥0.5 ISU) was present in most subjects everywhere. For regionally occurring pollen allergens (ragweed, birch, cypress), IgE sensitization was significantly associated with regional pollen exposure. For airborne allergens cross-reacting with food allergens, frequent IgG recognition was observed even in regions with low allergen prevalence (Bet v 1) or for allergens less frequently recognized by IgE (profilins). Conclusions The variability in allergen-specific IgE and IgG frequencies depends on exposure, route of exposure, and overall immunogenicity of the allergen. Allergen contact by the oral route might preferentially induce IgG responses.
Asthma, rhinitis, and eczema are complex diseases with multiple genetic and environmental factors interlinked through IgE-associated and non–IgE-associated mechanisms. Mechanisms of the Development ...of ALLergy (MeDALL; EU FP7-CP-IP; project no: 261357; 2010-2015) studied the complex links of allergic diseases at the clinical and mechanistic levels by linking epidemiologic, clinical, and mechanistic research, including in vivo and in vitro models. MeDALL integrated 14 European birth cohorts, including 44,010 participants and 160 cohort follow-ups between pregnancy and age 20 years. Thirteen thousand children were prospectively followed after puberty by using a newly standardized MeDALL Core Questionnaire. A microarray developed for allergen molecules with increased IgE sensitivity was obtained for 3,292 children. Estimates of air pollution exposure from previous studies were available for 10,000 children. Omics data included those from historical genome-wide association studies (23,000 children) and DNA methylation (2,173), targeted multiplex biomarker (1,427), and transcriptomic (723) studies. Using classical epidemiology and machine-learning methods in 16,147 children aged 4 years and 11,080 children aged 8 years, MeDALL showed the multimorbidity of eczema, rhinitis, and asthma and estimated that only 38% of multimorbidity was attributable to IgE sensitization. MeDALL has proposed a new vision of multimorbidity independent of IgE sensitization, and has shown that monosensitization and polysensitization represent 2 distinct phenotypes. The translational component of MeDALL is shown by the identification of a novel allergic phenotype characterized by polysensitization and multimorbidity, which is associated with the frequency, persistence, and severity of allergic symptoms. The results of MeDALL will help integrate personalized, predictive, preventative, and participatory approaches in allergic diseases.
In hypertrophic cardiomyopathy (HC), electrocardiographic (ECG) changes have been postulated to be an early marker of disease, detectable in sarcomere mutation carriers when left ventricular (LV) ...wall thickness is still normal. However, the ECG features of mutation carriers have not been fully characterized. Therefore, we systematically analyzed ECGs in a genotyped HC population to characterize ECG findings in mutation carriers (G+) with and without echocardiographic LV hypertrophy (LVH), and to evaluate the accuracy of ECG findings to differentiate at-risk mutation carriers from genetically unaffected relatives during family screening. The ECG and echocardiographic findings were analyzed from 213 genotyped subjects (76 G+/LVH−, 57 G+/LVH+ overt HC, 80 genetically unaffected controls). Cardiac magnetic resonance imaging was available on a subset. Q waves and repolarization abnormalities (QST) were highly specific (98% specificity) markers for LVH− mutation carriers, present in 25% of G+/LVH− subjects, and 3% of controls (p <0.001). QST ECG abnormalities remained independently predictive of carrying a sarcomere mutation after adjusting for age and impaired relaxation, another distinguishing feature of G+/LVH− subjects (odds ratio 8.4, p = 0.007). Myocardial scar or perfusion abnormalities were not detected on cardiac magnetic resonance imaging in G+/LVH− subjects, irrespective of the ECG features. In overt HC, 75% had Q waves and/or repolarization changes, but <25% demonstrated common isolated voltage criteria for LVH. In conclusion, Q waves and repolarization abnormalities are the most discriminating ECG features of sarcomere mutation carriers with and without LVH. However, owing to the limited sensitivity of ECG and echocardiographic screening, genetic testing is required to definitively identify at-risk family members.
Mechanisms of the Development of Allergy (MeDALL), a Seventh Framework Program European Union project, aims to generate novel knowledge on the mechanisms of initiation of allergy. Precise phenotypes ...of IgE-mediated allergic diseases will be defined in MeDALL. As part of MeDALL, a scientific seminar was held on January 24, 2011, to review current knowledge on the IgE-related phenotypes and to explore how a multidisciplinary effort could result in a new integrative translational approach. This article provides a summary of the meeting. It develops challenges in IgE-related phenotypes and new clinical and epidemiologic approaches to the investigation of allergic phenotypes, including cluster analysis, scale-free models, candidate biomarkers, and IgE microarrays; the particular case of severe asthma was reviewed. Then novel approaches to the IgE-associated phenotypes are reviewed from the individual mechanisms to the systems, including epigenetics, human in vitro immunology, systems biology, and animal models. The last chapter deals with the understanding of the population-based IgE-associated phenotypes in children and adolescents, including age effect in terms of maturation, observed effects of early-life exposures and shift of focus from early life to pregnancy, gene-environment interactions, cohort effects, and time trends in patients with allergic diseases. This review helps to define phenotypes of allergic diseases in MeDALL.
Abstract In patients with ST-elevation myocardial infarction (STEMI) the amount of myocardial area at risk (MaR) indicates the maximal potential loss of myocardium if the coronary artery remains ...occluded. During the time course of infarct evolution ischemic MaR is replaced by necrosis, which results in a decrease in ST segment elevation and QRS complex distortion. Recently it has been shown that combining the electrocardiographic (ECG) Aldrich ST and Selvester QRS scores result in a more accurate estimate of MaR than using either method alone. Therefore, we hypothesized that the combined Aldrich and Selvester score, indicating MaR, is stable until myocardial reperfusion therapy. In a retrospective analysis of a study population of 114 patients, 33 patients were included. The combined Aldrich and Selvester score was determined in ECGs recorded in the ambulance (ECG1) and in the hospital before reperfusion (ECG2). The combined Aldrich and Selvester score was considered stable if the difference between ECG1 and ECG2 was < 4.5-percentage point. Stability of the combined Aldrich and Selvester score was observed in 12/33 patients (36.4%), and in regards to anterior and inferior ST elevation in 4/14 patients (28.6%) and 8/19 patients (42.1%), respectively. The median time between the recording of ECG1 and ECG2 was 75 minutes, however the changes in ECG scores were independent of the time between ECG recordings. Patients not meeting the stability criterion either had a decrease (9 patients) or increase (12 patients) of the combined Aldrich and Selvester score. In conclusion, the ECG estimated MaR was stable between the earliest recording time and initiation of reperfusion treatment only in a subgroup of the patients with STEMI. The findings of this study may suggest heterogeneity in regards to the development of the MaR and could indicate a potential need for differentiation in the acute treatment.
PDF
