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Background: IgE antibodies to cross-reactive carbohydrate determinants (CCD) are usually clinically irrelevant but they can be a cause of false positive outcomes of allergen-specific IgE tests in vitro. Their prevalence and levels have been so far cross-sectionally examined among adult allergic patients and much less is known about their origins and relevance in childhood., Methods: We examined CCD with a cross-sectional approach in 1263 Italian pollen allergic children (Panallergen in Paediatrics, PAN-PED), as well as with a longitudinal approach in 612 German children (Multicenter Allergy Study, MAS), whose cutaneous and IgE sensitization profile to a broad panel of allergen extracts and molecules was already known. The presence and levels of IgE to CCD were examined in the sera of both cohorts using bromelain (MUXF3) as reagent and a novel chemiluminescence detection system, operating in a solid phase of fluorescently labelled and streptavidin-coated paramagnetic microparticles (NOVEOS, HYCOR, USA)., Results: IgE to CCD was found in 22% of the Italian pollen allergic children, mainly in association with an IgE response to grass pollen. Children with IgE to CCD had higher total IgE levels and were sensitized to more allergenic molecules of Phleum pratense than those with no IgE to CCD. Among participants of the German MAS birth cohort study, IgE to CCD emerged early in life (even at pre-school age), with IgE sensitization to group 1 and 4 allergen molecules of grasses, and almost invariably persisted over the full observation period., Conclusions: Our results contribute to dissect the immunological origins, onset, evolution and risk factors of CCD-sIgE response in childhood, and raise the hypothesis that group 1 and/or 4 allergen molecules of grass pollen are major inducers of these antibodies through an antigen-specific, T-B cell cognate interaction., (© 2024 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.)

Objective: We present an overview of important results obtained during the first 20 years of the Multicenter Allergy Study (MAS), one of the first and longest-running population-based birth cohorts focusing on asthma and allergy., Data Source/study Selections: The MAS is an observational population-based allergy-risk enriched cohort of 1,314 newborns enrolled in Germany in 1990. Assessments of various lifestyle and environmental exposures took place at 19 points, including 9 clinical visits for physical examinations and biosampling up to age 20 years., Results: A positive allergic family history was a strong predictor of asthma from childhood up to adulthood, more so for allergic multimorbidity than single allergic entities. For asthma prevalence, the early male preponderance shifted toward females during adolescence, leading to a sex-balanced distribution by age 20 years. Eczema prevalence switched toward a clear and persisting female predominance, whereas allergic rhinitis continued to affect more males up to age 20 years. The immunoglobulin (Ig) E antibody response to grass evolved in many allergic children from a simple, often mono- and oligomolecular to a polymolecular sensitization stage ("molecular spreading"). Indoor allergen exposure increased the risk for specific sensitization, which was linked to asthma and impaired lung function at early school-age. Moreover, the MAS birth cohort has made important contributions to the investigation of genetic factors in the manifestation of clinical subphenotypes and in the long-term temporal trajectory of allergic diseases., Conclusion: Follow-up assessments over 2 decades provided new insights into risk factors and predictors for eczema, rhinitis, and asthma up to adulthood to develop better prevention strategies., (Copyright © 2018 American College of Allergy, Asthma 8 Immunology. Published by Elsevier Inc. All rights reserved.)

Background: In early childhood, the allergen-specific IgG repertoire is mainly directed to animal and vegetable food molecules and infrequently to airborne molecules. It is unknown whether this early pattern is maintained throughout childhood., Objective: To investigate the evolution of IgG and IgE responses to a broad panel of allergenic molecules from birth to age 10 years., Methods: We examined the sera collected between birth and age 10 years from participants in the German Multicentre Allergy Study, a birth cohort born in 1990. The IgE (cutoff ≥0.30 ISU) and IgG (cutoff ≥0.10 ISU) responses to 35 genuine allergenic molecules were measured with a multiplex microarray approach (ImmunoCAP ISAC™)., Results: IgE responses were mostly directed against a restricted group of airborne molecules, with a sequence and prevalence hierarchy (Phl p 1> Bet v 1> Fel d 1> Phl p 5> Der p 2> Der p 1) largely maintained over time. Conversely, the IgG repertoire was much broader, starting with animal foodborne, then spreading to vegetable foodborne and finally to airborne molecules. A strong and persistent IgG response to a given airborne molecule almost invariably preceded or accompanied an IgE response to that molecule., Conclusions: The evolution of IgG and IgE responses throughout childhood differs widely at population level. IgG responses are mostly directed to animal food allergens, while IgE responses are dominated by airborne allergens. However, a strong IgG response almost invariably precedes or accompanies the appearance of IgE to the same molecule in specifically sensitized subjects., (© 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Previous studies of serum total IgE (t-IgE) were not able to discriminate well-enough atopic from non-atopic subjects, that is, with or without serum-specific IgE antibodies to allergens., Objectives: To model growth curves of the total IgE levels in children without atopic sensitization (hereafter defined as "normal" t-IgE levels) and to test their usefulness in predicting atopic sensitization., Methods: The German Multicentre Allergy Study (MAS), a birth cohort with 1314 recruited newborns, began in 1990 and examined the participants until age 20 years. Total and specific IgE (t-IgE, s-IgE) were analyzed with a fluorescent enzyme immunoassay ImmunoCAP (TFS, Sweden) at ages 1, 2, 3, 5, 6, 7, 10, 13, and 20 years. Participants were classified as "never atopic" if all their available serum samples had negative response (cutoff: <0.35 kU A /L) for s-IgE to the nine common foodborne and airborne allergenic extracts (milk, egg, soy, wheat, house dust mite, cat, dog, birch, and grass) tested in the MAS birth cohort. By contrast, participants were defined as atopic if they had, for at least at one available serum sample, s-IgE≥0.35 kU A /L to at least one allergenic extract tested. The evolution of t-IgE levels in the "never atopic" children was described by growth curves, estimated by exploiting a quantile regression model. A "reference" percentile, based on the t-IgE value measured at age 5 years, was assigned to each child with no IgE sensitization at that age. Upward deviations from the own "reference" quantile of t-IgE in atopic and "never atopic" children were calculated and a ROC analysis was used to identify the best cutoff point for predicting atopic sensitization., Results: Overall, 1113 of 1314 children were included in this analysis. Of these, 469 were "never atopic" and 644 atopic. Quantile trajectories of t-IgE levels in "never atopic" subjects were stable from 5 years of age, increased to a plateau at age 10-13 years, and decreased slightly afterward. The onset of atopic s-IgE responses was characterized by an upward deviation of serum t-IgE levels from their "reference" trajectory. T-IgE quantiles predicted the onset of atopy with high efficiency (AUC>80%). ROC analysis showed that deviations from the t-IgE level "reference" quantile above 0.32, 0.41, 0.42, 0.30, and 0.58 kU/L (log-units) at 6, 7, 10, 13, and 20 years of age, respectively, predicted an atopic sensitization., Conclusion: The growth curves of "normal" serum t-IgE concentrations were estimated in "never atopic" children; for each individual who was non-atopic at 5 years of age a "reference" quantile was identified that represented the individual's "normal" level of t-IgE production. Upward deviations of observed t-IgE levels from the own "reference" quantile, from 6 to 20 years of age, predicted at each year the occurrence of atopic sensitization., Clinical Implications: The trajectory of t-IgE levels can be elaborated since age 5 years in non-atopic children. A child whose t-IgE levels are consistently higher than those predicted by his/her growth curve may have developed atopic sensitization., (© 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: The evolution of the IgE response to the numerous allergen molecules of Dermatophagoides pteronyssinus is still unknown., Objectives: We sought to characterize the evolutionary patterns of the IgE response to 12 molecules of D pteronyssinus from birth to adulthood and to investigate their determinants and clinical relevance., Methods: We investigated the clinical data and sera of 722 participants in the German Multicenter Allergy Study, a birth cohort started in 1990. Diagnoses of current allergic rhinitis (AR) related to mite allergy and asthma were based on yearly interviews at the ages of 1 to 13 years and 20 years. IgE to the extract and 12 molecules of D pteronyssinus were tested by means of ImmunoCAP and microarray technology, respectively, in sera collected at ages 1, 2, 3, 5, 6, 7, 10, 13, and 20 years. Exposure to mites at age 6 and 18 months was assessed by measuring Der p 1 weight/weight concentration in house dust., Results: One hundred ninety-one (26.5%) of 722 participants ever had IgE to D pteronyssinus extract (≥0.35 kU A /L). At age 20 years, their IgE recognized most frequently Der p 2, Der p 1, and Der p 23 (group A molecules; prevalence, >40%), followed by Der p 5, Der p 7, Der p 4, and Der p 21 (group B molecules; prevalence, 15% to 30%) and Der p 11, Der p 18, clone 16, Der p 14, and Der p 15 (group C molecules; prevalence, <10%). IgE sensitization started almost invariably with group A molecules and expanded sequentially first to group B and finally to group C molecules. Early IgE sensitization onset, parental hay fever, and higher exposure to mites were associated with a broader polymolecular IgE sensitization pattern. Participants reaching the broadest IgE sensitization stage (ie, ABC) had significantly higher risk of mite-related AR and asthma than unsensitized participants. IgE to Der p 1 or Der p 23 at age 5 years or less predicted asthma at school age., Conclusions: Parental hay fever and early exposure to D pteronyssinus allergens promote IgE polysensitization to several D pteronyssinus molecules, which in turn predicts current mite-related AR and current/future asthma. These results might inspire predictive algorithms and prevention strategies against the progression of IgE sensitization to mites toward AR and asthma., (Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Studies of a limited number of allergens suggested that nonsensitized children produce IgG responses mainly to foodborne allergens, whereas IgE-sensitized children also produce strong IgG responses to the respective airborne molecules., Objective: We sought to systematically test the hypothesis that both the route of exposure and IgE sensitization affect IgG responses to a broad array of allergenic molecules in early childhood., Methods: We examined sera of 148 children participating in the Multicentre Allergy Study, a birth cohort born in 1990. IgG to 91 molecules of 42 sources were tested with the ImmunoCAP Solid-Phase Allergen Chip (ISAC; TFS, Uppsala, Sweden). IgE sensitization at age 2 and 7 years was defined by IgE levels of 0.35 kU A /L or greater to 1 or more of 8 or 9 extracts from common allergenic sources, respectively., Results: The prevalence and geometric mean levels of IgG to allergenic molecules in nonsensitized children were lower at age 2 years than in IgE-sensitized children, and they were extremely heterogeneous: highest for animal food (87% ± 13%; 61 ISAC Standardized Units [ISU], [95% CI, 52.5-71.5 ISU]), intermediate for vegetable food (48% ± 27%; 13 ISU [95% CI, 11.2-16.1 ISU]), and lowest for airborne allergens (24% ± 20%; 3 ISU [95% CI, 2.4-3.4 ISU]; P for trend < .001 [for percentages], P for trend < .001 [for levels]). IgG 4 antibodies were infrequent (<5%) and contributed poorly (<3%) to overall IgG antibody levels. IgG responses at age 2 years were slightly more frequent and stronger among children with than in those without IgE sensitization at age 7 years., Conclusion: The children's repertoire of IgG antibodies at 2 years of age to a broad array of animal foodborne, vegetable foodborne, and airborne allergenic molecules is profoundly dependent on the route of allergen exposure and the child's IgE sensitization status and only marginally involves the IgG 4 isotype., (Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Allergic diseases [asthma, rhinitis and atopic dermatitis (AD)] are complex. They are associated with allergen-specific IgE and nonallergic mechanisms that may coexist in the same patient. In addition, these diseases tend to cluster and patients present concomitant or consecutive diseases (multimorbidity). IgE sensitization should be considered as a quantitative trait. Important clinical and immunological differences exist between mono- and polysensitized subjects. Multimorbidities of allergic diseases share common causal mechanisms that are only partly IgE-mediated. Persistence of allergic diseases over time is associated with multimorbidity and/or IgE polysensitization. The importance of the family history of allergy may decrease with age. This review puts forward the hypothesis that allergic multimorbidities and IgE polysensitization are associated and related to the persistence or re-occurrence of foetal type 2 signalling. Asthma, rhinitis and AD are manifestations of a common systemic immune imbalance (mesodermal origin) with specific patterns of remodelling (ectodermal or endodermal origin). This study proposes a new classification of IgE-mediated allergic diseases that allows the definition of novel phenotypes to (i) better understand genetic and epigenetic mechanisms, (ii) better stratify allergic preschool children for prognosis and (iii) propose novel strategies of treatment and prevention., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: In adults, subjects sensitized to Staphylococcus aureus enterotoxins (SE) seem to have an increased risk of asthma, whereas this association is less clear in childhood and adolescence. The primary aim of the present analysis was to examine the association between sensitization to SE and asthma at the age of 20 years., Methods: The German Multicentre Allergy Study recruited 1314 healthy newborns in 1990. We analyzed data from 61 asthmatics (based on at least two criteria: physician diagnosed asthma ever, wheezing in the last 12 months, asthma medication in the last 12 months) and 122 healthy study participants at age 20. In serum, specific Immunoglobulin E (IgE) to SE and common aeroallergens were measured. The association between asthma at age 20 and sensitization to SE was estimated by logistic regression models considering allergic, socio-demographic, and lifestyle factors as potential confounders., Results: Fifty-five percent of the included participants were female. At age 20, subjects sensitized to SE were more likely to have asthma than not-sensitized subjects: raw odds ratio (OR) 2.5, 95%-confidence interval (95%CI) [1.3-4.7]; adjusted OR 1.6, 95%CI [0.8-3.4]., Conclusion: Asthmatics at age 20 were more often sensitized to SE compared to controls. Our study may indicate a moderate relationship between SE-sensitization and asthma; however, this association attenuated after adjusting for potential confounders and was no longer statistically significant. Longitudinal investigations with SE-IgE measurements at different time points in larger samples are needed to explore the temporal manner of this relationship., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: An early IgE response to grass or birch pollen can anticipate seasonal allergic rhinitis to pollen later in life or remain clinically silent., Objective: To identify risk factors early in life that allow discriminating pathogenic from non-pathogenic IgE responses and contribute to the development of seasonal allergic rhinitis to grass pollen., Methods: The German Multicentre Allergy Study examined a birth cohort born in 1990. A questionnaire was yearly administered and blood samples collected at age 1,2,3,5,6,7,10,13 yr. The definition of the primary outcome grass- and birch-pollen-related seasonal allergic rhinitis (SARg, SARb) was based on nasal symptoms in June/July and April, respectively. Serum IgE antibodies to Phleum pratense and Betula verrucosae extracts were monitored with immune-enzymatic singleplex assays., Results: Of the 820 examined children, 177 and 148 developed SARg and SARb, respectively. Among healthy children aged 3 or more years, IgE to grass pollen was the strongest risk factor of SARg (OR 10.39, 95%CI 6.1-17.6, p < 0.001), while parental hay fever was the only risk factor in early childhood independently associated with future SARg (1 parent: OR 2.56, 95%CI 1.4-4.5, p < 0.001; 2 parents: OR 4.17, 95%CI 1.7-10.1) and SARb (1 parent OR: 5.21, 95%CI 2.20-12.4, p < 0.001; 2 parents: OR 8.02, 95%CI 2.0-32.9, p < 0.001). Parental hay fever was associated with an increase of the concentration of pollen-specific IgE in seropositive subjects, after the age of 6 and was also a hallmark of molecularly more complex specific IgE responses to grass or birch pollen at age 6 or older., Conclusions: Parental hay fever and specific IgE to grass and/or birch pollen are strong pre-clinical determinants and potentially good predictors of seasonal allergic rhinitis., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Eczema, rhinitis, and asthma often coexist (comorbidity) in children, but the proportion of comorbidity not attributable to either chance or the role of IgE sensitisation is unknown. We assessed these factors in children aged 4-8 years., Methods: In this prospective cohort study, we assessed children from 12 ongoing European birth cohort studies participating in MeDALL (Mechanisms of the Development of ALLergy). We recorded current eczema, rhinitis, and asthma from questionnaires and serum-specific IgE to six allergens. Comorbidity of eczema, rhinitis, and asthma was defined as coexistence of two or three diseases in the same child. We estimated relative and absolute excess comorbidity by comparing observed and expected occurrence of diseases at 4 years and 8 years. We did a longitudinal analysis using log-linear models of the relation between disease at age 4 years and comorbidity at age 8 years., Findings: We assessed 16 147 children aged 4 years and 11 080 aged 8 years in cross-sectional analyses. The absolute excess of any comorbidity was 1·6% for children aged 4 years and 2·2% for children aged 8 years; 44% of the observed comorbidity at age 4 years and 50·0% at age 8 years was not a result of chance. Children with comorbidities at 4 years had an increased risk of having comorbidity at 8 years. The relative risk of any cormorbidity at age 8 years ranged from 36·2 (95% CI 26·8-48·8) for children with rhinitis and eczema at age 4 years to 63·5 (95% CI 51·7-78·1) for children with asthma, rhinitis, and eczema at age 4 years. We did longitudinal assessment of 10 107 children with data at both ages. Children with comorbidities at 4 years without IgE sensitisation had higher relative risks of comorbidity at 8 years than did children who were sensitised to IgE. For children without comorbidity at age 4 years, 38% of the comorbidity at age 8 years was attributable to the presence of IgE sensitisation at age 4 years., Interpretation: Coexistence of eczema, rhinitis, and asthma in the same child is more common than expected by chance alone-both in the presence and absence of IgE sensitisation-suggesting that these diseases share causal mechanisms. Although IgE sensitisation is independently associated with excess comorbidity of eczema, rhinitis, and asthma, its presence accounted only for 38% of comorbidity, suggesting that IgE sensitisation can no longer be considered the dominant causal mechanism of comorbidity for these diseases., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: IgE sensitization against grass pollen is a cause of seasonal allergic rhinitis., Objective: We sought to investigate the evolution at the molecular level and the preclinical predictive value of IgE responses against grass pollen., Methods: The German Multicentre Allergy Study examined a birth cohort born in 1990. A questionnaire was administered yearly, and blood samples were collected at 1, 2, 3, 5, 6, 7, 10, and 13 years of age. Grass pollen-related seasonal allergic rhinitis (SARg) was diagnosed according to nasal symptoms in June/July. Serum IgE antibodies to Phleum pratense extract and 8 P pratense molecules were tested with immune-enzymatic singleplex and multiplex assays, respectively., Results: One hundred seventy-seven of the 820 examined children had SARg. A weak monomolecular/oligomolecular IgE response to P pratense was observed very frequently before SARg onset. These initial IgE responses increased in concentration and molecular complexity during the preclinical and clinical process. A typical progression of IgE sensitization was observed: Phl p 1 (initiator in >75% of cases); then Phl p 4 and Phl p 5; then Phl p 2, Phl p 6, and Phl p 11; and then Phl p 12 and Phl p 7. At age 3 years, IgE sensitization predicted SARg by age 12 years (positive predictive value, 68% [95% CI, 50% to 82%]; negative predictive value, 84% [95% CI, 80% to 87%]). At this preclinical prediction time, the number of recognized molecules and the serum levels of IgE to P pratense were significantly lower than at 3 or more years after SARg onset., Conclusions: The IgE response against grass pollen molecules can start years before disease onset as a weak monosensitization or oligosensitization phenomenon. It can increase in serum concentration and complexity through a "molecular spreading" process during preclinical and early clinical disease stages. Testing IgE sensitization at a preclinical stage facilitates prediction of seasonal allergic rhinitis at its molecular monosensitization or oligosensitization stage., (Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

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., (Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Background: Allergic rhinoconjunctivitis and asthma evolve dynamically throughout childhood. Yet, data on the evolution of serum levels of IgE antibodies against airborne allergens throughout the first decade of life are scarce., Objective: To describe the patterns of new and persistent sensitization against airborne allergens including remission from birth to 10 years of age and the long-term clinical outcomes up to the age of 13 years., Methods: In 273 children from the Multi-Centre Allergy Study, a German birth cohort, IgE levels were determined against airborne allergens (Dermatophagoides pteronyssinus, cat and dog dander, birch and grass species pollens) at 2, 5, 7, and 10 years of age (ImmunoCAP, Phadia); allergic rhino-conjunctivitis and asthma were ascertained at the 13 years of age through a standardized questionnaire (International Study of Asthma and Allergies in Childhood)., Results: The prevalence of sensitization to each allergen increased steadily throughout childhood, and a hierarchy of sensitization prevalence (grass>birch>mites>cat>dog) was maintained from 5 years of age onwards. A mono-sensitization state was relatively short (measurable half-life=3 years) as additional sensitizations were acquired frequently, and relatively soon after the first one. Remission of weak sensitization (UNICAP classes 1-2) was also quite frequent, especially before 5 years of age. By contrast, stronger IgE responses (>3.5 kU/L) were invariably persistent. Early sensitization was associated with a higher tendency for poly-sensitization at 10 years of age and allergic rhino-conjunctivitis and/or asthma at 13 years of age., Conclusions: IgE responses against airborne allergens undergo dynamic changes throughout childhood, with a high frequency of new sensitization or remission. The long-term persistence and the clinical impact of IgE responses are affected by the intensity of IgE sensitization and the age of its onset.

Background: The development and the quantitative relationship between allergen-specific IgE (S-IgE) responses and total IgE (T-IgE), during childhood and adolescence have not been described and understood in detail. The objective of this study was to describe and compare the longitudinal trends of serum levels of S-IgE and T-IgE during childhood., Methods: We analysed data from participants in the MAS birth cohort study at 2, 5, 7 and 10 years of age (n = 273) and at 1, 3, 5, 6, 7, 10 and 13 years (n = 84). Total-IgE and the overall level of specific-IgE against nine locally relevant airborne and food allergens were determined by FEIA (ImmunoCAP). Allergic rhino-conjunctivitis and asthma were ascertained by questionnaires., Results: Longitudinal patterns of T-IgE levels from age 1 to 13 years were highly heterogeneous (declining, flat or increasing with different profiles). From 5 years of age, logarithmic (log(10)) transformed values of T-IgE and of S-IgE levels tend to follow a parallel trend, so that their relation remained constant throughout school age. A flat trend of T-IgE vs a constantly increasing trend of T-IgE was associated with a low or, respectively, high rate of wheezing at 13 years of age., Conclusions: Beginning at the age of 5 years, total serum IgE levels in children from an industrialized country evolved in parallel with overall S-IgE levels. Therefore, variations in T-IgE levels at school age closely reflect variations in overall S-IgE levels. Further studies are required to strengthen the biological and clinical implication of this novel finding.

Background: Exposure and sensitization to pet allergens are associated with allergic asthma in children. Conflicting data have emerged regarding the potential benefit of air cleaners with respect to a reduction of indoor pet allergens and bronchial hyperresponsiveness (BHR)., Methods: In a randomized controlled trial 36 asthmatic children with sensitization to cat and/or dog and significant exposure to cat and/or dog allergen (Fel d 1 and/or Can f 1 >500 ng/g of carpet dust) were included in order to study the effect of high-efficiency particulate arresting (HEPA) air cleaners placed in the living room and bedroom compared with the effect of sham air cleaners. Patients were allocated to two groups: group 1 exposed to active filters and group 2 exposed to sham filters. At month 0, after 6 months and after 12 months, pulmonary function testing and cold air challenge were performed, serum eosinophil cationic protein (ECP) and specific IgE to seven aeroallergens were determined, and carpet dust samples and filters were collected. Major pet allergen concentrations (Fel d 1, Can f 1) were determined in filters and bulk dust samples., Results: Thirty patients completed the study. After 6 and 12 months, there was no significant change in delta FEV(1) after cold air challenge, or in the use of medication and serum ECP levels. However, there was a trend in the active group towards an improvement of bronchial hyperresponsiveness, whereas the sham filter group showed a deterioration of BHR., Conclusion: Although HEPA air cleaners retained airborne pet allergens, no effect on disease activity or allergen concentrations in bulk dust samples was observed in this study., ((c) 2008 S. Karger AG, Basel.)

Wheezing and eczema are common symptoms in young children and it is important to disclose sensitization for correct management. The objective of this study was to assess the diagnostic values of Phadiatop Infant, an in vitro test for graded determination of immunoglobulin E (IgE) antibodies to food and inhalant allergens. One-hundred and forty-nine children (median age 1.4 yr) with symptoms of wheezing (51%) eczema (28%) or a combination of both (21%) were classified as atopic or non-atopic based on case history, atopic history, physical examination and determination of IgE antibodies. The clinical performance of Phadiatop Infant was evaluated for 145 children against this classification in a blinded manner to the allergist. Fifty-one children were classified as atopic of which Phadiatop Infant identified 49. Ninety-four were non-atopic of which the test identified 90. This resulted in a sensitivity of 96%, a specificity of 96%, a positive and a negative predictive value of 94% and 98%, respectively. Logistic regression showed that probability had to be assessed as atopic increased with increasing Phadiatop Infant values. These results suggest that Phadiatop Infant can be recommended as an adjunct to the clinical information in the differential diagnosis on IgE-mediated allergy in young children. The test thus provides an opportunity for early correct diagnosis and identification of subjects at risk for whom intervention may be necessary.

Background: IgE sensitization to soy and wheat is classified as 'primary' when generated by food ingestion and 'secondary' when it as a consequence of primary sensitization to cross-reacting pollen antigens via inhalation. The age-specific relevance of these categories of sensitization throughout childhood is unknown., Objective: To monitor the natural course of IgE sensitization against common food allergens in childhood in relation to sensitization against cross-reactive airborne allergens., Methods: The German Multi-Centre Allergy Study with follow-up from birth to age 13 recruited initially 1314 children. IgE antibody levels against cow's milk, hen's egg, soy, wheat, mites, cat and dog dander, birch and grass pollens were tested. Longitudinal data were analysed from the 273 children with sera obtained at age 2, 5, 7 and 10 years of age., Results: The point prevalence of sensitization (>1.0 kU/L) to milk and egg allergens progressively decreased from about 4% at 2 years to <1% at 10 years. By contrast, the prevalence of IgE to wheat and soy progressively increased with age, from 2% to 7% (soy) and from 2% to 9% (wheat). At 10 years of age, IgE to grass pollen was detected in 97% and 98% of the children reacting against soy and wheat, respectively; IgE to birch pollen was observed in 86% and 82% of the children reacting against soy and wheat, respectively. Early IgE sensitization to soy or wheat preceded that to grass or birch pollen in only 4% and 8% of participants sensitized to soy and wheat, respectively., Conclusion: IgE sensitization to soy and wheat is relatively uncommon and mostly primary in early infancy, more frequent and mostly secondary to pollen sensitization at school age. Clinical Implications Awareness should be raised to avoid unnecessary diet restrictions due to the high frequency of clinically irrelevant, secondary sensitization to soy and wheat in schoolchildren with pollinosis.

Background: Some studies have suggested that supplementation of food with lactobacilli may prevent or improve atopic dermatitis in children. This study was designed to investigate the therapeutic effect of Lactobacillus rhamnosus GG (LGG) as a food supplement in infants suffering from atopic dermatitis., Methods: Infants aged 3-12 months suffering from mild-to-moderate atopic dermatitis (severity scoring of atopic dermatitis or SCORAD index of 15-40) without current antiinflammatory treatment were randomized to receive LGG (5 x 10(9) colony forming units b.i.d.) or placebo as a food supplement for 12 weeks. Severity scoring of atopic dermatitis index and use of hydrocortisone 1% ointment as rescue medication (2 points per application) were recorded at 4, 8, and 12 weeks of treatment and combined as symptom load (SL)., Results: Fifty-four infants (LGG group, mean +/- SD SCORAD index 24.6 +/- 8.8) and 48 infants (placebo group, SCORAD index 23.6 +/- 7.8) were randomized and completed the treatment period (intention-to-treat analysis). Symptom load generally improved over time at 4 weeks (LGG vs placebo, 23.8 +/- 12.4 vs 20.6 +/- 9.9), 8 weeks (22.5 +/- 14.6 vs 17.9 +/- 13.1), and 12 weeks (19.6 +/- 15.4 vs 15.1 +/- 12.1), without statistically significant group differences. When stratified for age, eczema severity or use of rescue medication, no statistically significant group differences, in improvement, were found. No significant group differences were found for the use of rescue medication (0.8 +/- 45.0 g vs 3.5 +/- 29.8 g), increase in mean logarithmic total serum IgE (0.17 +/- 0.30 kU/l vs 0.26 +/- 0.45 kU/l), and newly developed allergic sensitization against hen's egg or cow's milk (18.8%vs 10.0%)., Conclusion: This placebo-controlled trial showed no therapeutic effect of LGG against mild-to-moderate atopic dermatitis in infancy.

Atopic manifestations may be present from infancy to adolescence. Atopic dermatitis represents the first clinical manifestation followed by allergic symptoms of the upper or lower airways. IgE responses to alimentary or environmental allergens are hallmarks of atopy in childhood. Characteristically infantile IgE responses to cow's milk and hen's egg are the first immunological markers of atopy. In many cases they are followed by IgE responses to indoor or outdoor allergens, which suggests a high risk for the development of persistent asthma in childhood. During recent years a variety of genes for both asthma and atopic dermatitis have been described. Infantile diet, early exposure to environmental allergens and a variety of environmental and lifestyle factors may act as strong modulators of atopy during the first decade of life.

Background: Many environmental factors influence the concentration of total serum IgE (tIgE); however, tIgE synthesis is believed to be under strong genetic influence. Multiple genetic studies on tIgE regulation have been performed. For these population-based studies tIgE was commonly determined at one time-point, assuming that tIgE phenotypes (adjusted for age and gender) are stable over time., Objective: We assessed correlations of tIgE levels from birth to the age of 10 years in the birth cohort MAS (Multicenter Allergy Study; n=1314)., Materials and Methods: We determined cord-blood IgE levels, total and specific IgE at the age of 1, 2, 3, 5, 6, 7, and 10 years. Spearman correlation coefficients were calculated for tIgE at different time-points. All analyses were performed in the entire cohort, adjusted for gender, as well as in non-atopic children only., Results: tIgE percentiles increased steadily from birth to the age of 10 years with higher values for boys than for girls at each time-point. tIgE values from birth to 3 years of age correlated poorly with tIgE levels at 10 years (r<0.5). However, good correlations (r>0.8) were observed for tIgE concentrations at 6, 7 and 10 years. The same results were observed when the analyses were limited to non-atopic children., Conclusion: In childhood, tIgE levels underlie remarkable variation over time even in the absence of atopy. For cross-sectional population-based genetic and epidemiologic studies, tIgE values of children <5 years should be interpreted with caution since these values correlate poorly with tIgE levels later in life.

Background: Among many published studies of specific IgE response or atopy, only a few showed positive marginal effects for 6 potentially functional single nucleotide polymorphisms (SNPs; C-590T in the IL4 gene, C-1055T and Arg130Gln in the IL13 gene, and Ile50Val, Ser478Pro, and Gln551Arg in the IL4RA gene). SNPs were commonly considered individually, and therefore the true effect could be masked by other genes or environmental factors., Objective: We tested the relationship between these 6 SNPs and sensitization to food, mite, cat, and outdoor allergens in unrelated German children drawn from the Multicenter Atopy Study. Gene-gene and gene-environment interactions were also evaluated., Methods: Multiple logistic regression models were used for the analyses of 4 sensitization outcomes., Results: The variant C-1055T was significantly associated with increased risk of sensitization to food and outdoor allergens, with odds ratios of 3.49 (95% CI, 1.52-8.02) and 2.27 (95% CI, 1.04-4.94), respectively. The effects of the TT genotype on food sensitization appear to depend on variants in the IL4RA gene, in which marginally significant interaction terms were observed. Significant evidence supported an interaction between exposure to maternal smoking and variant Gln551Arg on risk of cat sensitization. In addition, we found that the effect of variant C-590T on sensitization to mite depended on Der p 1 allergen levels in carpet dust samples., Conclusions: These findings not only suggested that variants in the IL4, IL13, and IL4RA genes play an important role in controlling specific IgE response but also strengthened our understanding of gene-gene and gene-environment interaction on the development of specific sensitization in this study population.

Background: Increased total serum IgE levels are a common characteristic of atopic disorders. Six potentially functional variants, including C-590T in the IL4 gene, C-1055T and Arg130Gln in the IL13 gene, and Ile50Val, Ser478Pro, and Gln551Arg in the IL4RA gene, have been evaluated for their involvement in the control of total serum IgE levels and related atopic disorders, but the results of these studies have been inconsistent., Objective: We examined whether these 6 variants had genotypic effects on total serum IgE levels in 823 unrelated German children from a large infant cohort, the German Multicenter Atopy Study., Methods: Marginal effect models were used for the analyses of the repeated IgE measurements. Weighted linear regression and family-based tests of association were performed to minimize the possibility of spurious effects caused by selection bias or confounding on the basis of ethnic background., Results: There are significant associations between increased total serum IgE levels and 2 variants in the IL13 gene (P <.005 and.0002 for Arg130Gln and C-1055T, respectively). These genetic effects are unlikely to be due to solely linkage disequilibrium between 2 polymorphisms, population stratification, or nonrepresentative samples. In addition, exposure to maternal smoking appears to modify the above effects on total serum IgE levels. However, no statistical association was observed between this quantitative phenotype and the other 4 variants examined., Conclusion: These findings suggest that variants C-1055T and Arg130Gln of the IL13 gene might play an important role on total serum IgE production in this study population.

Pertussis (P) toxin acts as adjuvant for IgE formation against simultaneously administered Ags in animal models. P vaccination may also have an adjuvant impact on IgE formation against coadministered diphtheria (D) and tetanus (T) Ags in humans. Sera of 103 D-T-P-immunized and 319 D-T-immunized children aged 2 years were analyzed for IgE, IgG4, and IgG to D and T (radioallergosorbent test), total IgE and IgE against common inhalant allergens (CAP radioallergosorbent test fluoroenzyme immunoassay). Fewer D-T-P- than D-T-immunized children had sera positive for T-IgE (12.6 vs 53.6%, p < 0.001), T-IgG4 (71.6 vs 89.2%, p < 0.001), D-IgE (31.0 vs 70.5%, p < 0.001), and D-IgG4 (85.2 vs 93.4%, p = 0.039). Suppression of T-IgE was not dependent on the cutoff chosen for a positive test result, but was dependent on the proportion of D-T immunizations given with P. The risk for sensitization to common environmental allergens did not differ (odds ratio 0.953, 95% confidence interval 0.815-1.114). No significant differences between D-T- and D-T-P-immunized children were found with regard to T-IgG or D-IgG. In summary, IgE and IgG4 (but not IgG) serum levels to coadministered D- and T-Ags are suppressed among P-immunized children as compared with nonimmunized children. These results suggest that the presence of a microbial product during Ag exposure can down-regulate an IgE/IgG4 response in humans.

Objective: Total serum IgE percentiles were derived for a population-based sample of 4082 white children from Germany by weighted analysis of measurements from the Multicenter Allergy Study cohort., Methods: The children of a prospective birth cohort were selected from a complete 1-year sample of newborns in 6 obstetric departments in 1990. Total IgE was determined at 1, 2, 3, 5, and 6 years of age in 1160 newborns of the cohort. By weighting these measurements for sex, atopic family history, and elevated cord blood IgE, total serum IgE percentiles were estimated for the original population-based sample of 4082 children., Results: IgE levels increased by age (P <.0001). We found statistically significant higher total IgE values in boys than in girls at each age (P <.05). Within the group of atopic children, this sex difference was not statistically significant., Conclusion: Our estimates of total serum IgE levels for a large population-based sample were lower than most values previously reported. We suggest that for both clinical and epidemiologic and genetic studies, IgE values should be expressed with percentiles.

For screening atopy risk in 6401 (84%) of all infants born during the year 1990 in six obstetric departments of five German cities, cord-blood IgE values were determined with CAP-RAST-FEIA. After cases with elevated IgA values had been excluded, 25% of the values were above the detection limit of 0.35 kU/l, and 8.5% were above 0.9 kU/l. Boys had significantly higher values than girls (P < 0.001). The distribution of values was significantly different for different nationalities of mothers (P < 0.001). The percentage of elevated values (> 0.9 kU/l) increased significantly with the number of close family members with atopic history (P < 0.001). Regarding the atopic history of the father, siblings, and mother separately, only the mother's history had a significant association with the cord-blood IgE class (P < 0.001). The IgE values of 81 twin pairs correlated significantly with a coefficient of r = 0.4909 (P < 0.001). The smoking history of the parents during pregnancy showed an association with cord-blood IgE values (P < 0.02). No significant association could be shown between cord-blood IgE distribution and other variables, i.e., gestational age, birth size, birth modus, Apgar score, cord-blood pH value, neonatal problems, parity, age of the mother, medication during pregnancy, educational level of mother or father, time of year, or obstetric department. It is hypothesized that, in addition to some postpartum contamination or placental transfer of maternal IgE, cord-blood IgE values are also determined by the fetal immunologic reaction to intrauterine exposure to allergens and trigger factors, and by genetic influences.

Primary prevention strategies of allergy so far have been aimed to fight allergy causes, by avoiding risk factors and inhibiting their mechanisms of action. The results of trials testing food or airborne allergen avoidance as a prevention strategy were, however, rather disappointing. A reverse approach for primary prevention of allergies aims to facilitate exposure to protecting factors which promote the induction of immunologic tolerance against innocuous antigens. These factors are associated with farming environment and a ‘traditional lifestyle’, but identification of these factors is quite difficult. Major candidates include food-borne microbes, helminths or their components, which are able to stimulate mucosal immunity, particularly in the gut. Similarly, new preventive and therapeutic strategies are being tested to induce specific food-allergen oral tolerance through the ingestion of progressively increasing doses of the offending food. This shifting of allergy prevention research from avoidance to tolerance induction will hopefully allow us to reverse the epidemic trend of allergy diseases. [ABSTRACT FROM AUTHOR]