Dynamic evolution of serum immunoglobulin E to airborne allergens throughout childhood: results from the Multi-Centre Allergy Study birth cohort

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.     

Common variants in FCER1A influence total serum IgE levels from cord blood up to six years of life

Background:  In a recent genome wide scan, a functional promoter variant (rs2251746) in the gene encoding the alpha chain of the high affinity receptor for immunoglobulin E (IgE) (FCER1A) was identified as major determinant of serum IgE levels.
Objective:  The aim of this study was to investigate the role of rs2251746 on total IgE levels measured at different stages of life from birth (cord blood) up to the age of 6 and to evaluate its interaction with the environmental influences in two German birth cohorts.
Method:  Data from two German birth cohorts were analysed ( n  = 1043 for the LISA cohort and n  = 1842 for the GINI cohort). In the studies, total serum IgE was measured from cord blood, and blood samples taken at the age of 2/3 and 6 years. In a subgroup of the LISA study, house dust samples were collected at age of 3 months and the amount of endotoxin was determined. Random effect models were used to analyse the longitudinal health outcomes.
Results:  In the two cohorts, the heterozygote and the rare homozygote of rs2251746 was consistently associated with lower total IgE levels from birth up to the age of 6 years with an allele-dose effect ( P  < 0.02 for blood samples taken at each time point in both cohorts). No interaction between the two FCER1A encoding gene and environmental exposures including endotoxin, worm infestation and day care centre attendance during early childhood were observed.
Conclusion:  Common variants in FCER1A strongly influence basal IgE production independently from environmental stimuli. These effects can be observed already in cord blood pointing to altered gene expression in foetus.     

Relationship between pretreatment specific IgE and the response to omalizumab therapy

Background:  Omalizumab, an anti-IgE antibody, has proven efficacy in patients with moderate-to-severe and severe persistent allergic (IgE-mediated) asthma. While previous analyses have had some limited success in predicting which patients will gain greatest benefit based on pretreatment baseline characteristics, it remains important to try to improve this predictability.
Methods:  Following a run-in phase, patients (12–75 years) inadequately controlled despite current therapy were randomized to receive omalizumab or placebo for 28 weeks in a double-blind, parallel-group, multicenter study (INNOVATE). Univariate analyses were performed to assess whether pretreatment specific IgE serum levels and related variables could be identified that were predictive of a response to omalizumab patients ( n  = 337) enrolled in INNOVATE. Response was measured via variables including exacerbations, QoL, FEV₁ and physicians' overall assessment.
Results:  A total of 305 patients (90.5%) were sensitive to more than one allergen and the majority of patients were positive to D1 Dermatophagoides pteronyssinus and D2 Dermatophagoides farinae . Patients with relatively high values of D1 or D2, but with these making a relatively low contribution to total specific IgE load, appeared to attain most benefit from omalizumab. However, no consistent predictive effect for omalizumab response was observed either for total specific IgE or levels of IgEs specific for individual allergens.
Conclusions:  Based on these data, pretreatment allergen-specific IgE levels do not provide any better prediction of response to treatment as compared with pretreatment total IgE. At present, the most reliable method of identifying patients who respond to omalizumab treatment remains a physician's assessment.     

Dietary antioxidant intake, allergic sensitization and allergic diseases in young children

Background:  Allergic diseases have risen in prevalence over recent decades. The aetiology remains unclear but is likely to be a result of changing lifestyle and/or environment. A reduction in antioxidant intake, consequent to reduced intake of fresh fruits and vegetables, has been suggested as a possible cause.
Objective:  To investigate whether dietary antioxidant intake at age 5 was related to atopy at 5 and 8 years of age amongst children in an unselected birth cohort.
Methods:  Children were followed from birth. Parents completed a validated respiratory questionnaire and children were  skin prick tested at 5 and 8 years of age. Serum IgE levels were measured at age 5. At age 5, antioxidant intake was assessed using a semi-quantitative food frequency questionnaire (FFQ). A nutrient analysis program computed nutrient intake, and frequency counts of foods high in the antioxidant vitamins A, C and E were assessed.
Results:  Eight hundred and sixty-one children completed both the respiratory and FFQ. Beta-carotene intake was associated with reduced risk of allergic sensitization at age 5 [0.80 (0.68–0.93)] and 8 [0.81 (0.70–0.94)]. In addition, beta-carotene intake was negatively associated with total IgE levels ( P  = 0.002). Vitamin E intake was associated with an increased risk of allergic sensitization [1.19 (1.02–1.39)], only at age 5. There was no association between antioxidant intakes and wheeze or eczema.
Conclusion:  Increased beta-carotene intake was associated with a reduced risk of allergic sensitization and lower IgE levels, in  5- and 8-year-old children. Dietary antioxidants may play a role in the development of allergic sensitization.     

IgE-binding and cross-reactivity of a new 41 kDa allergen of codfish

Background:   A 41-kDa IgE-reactive protein (p41) was purified from raw cod extract. This protein is homologous to an aldehyde phosphate dehydrogenase (APDH). The present study aims to evaluate the IgE-binding and the cross-reactivity of this protein in 13 patients allergic to codfish.
Methods:   IgE binding of sera from 13 patients allergic to codfish was tested by Sepharose RIA and by Western blot.
Results:   Among the 13 patients, only 4 had specific IgE to APDH detected by APDH-Sepharose RIA. The two patients who had the highest level of specific IgE to human APDH also had a class 5–6 CAP-RAST IgE level to codfish, but two other patients with a class 5 had a negative APDH-Sepharose IgE-RIA. Relative content of APDH was higher in extracts of commercial nonfrozen fish, compared to pre rigor mortis , post rigor mortis and frozen commercial codfish. A high homology of codfish APDH was found with the corresponding human enzyme. A significant inhibition of APDH-Sepharose by human and, to a lesser extent, by rabbit APDH was observed. Western blot of APDH codfish extract showed two bands at 41 and 36 kDa, respectively.
Conclusions:   We have characterized a new allergen from codfish, which had a high level of homology in different species. The p41 relative content of extracts from nonfrozen codfish was higher than in the other samples assessed.     

A high-affinity monoclonal anti-IgE antibody for depletion of IgE and IgE-bearing cells

Background:  We have identified a monoclonal anti-human immunoglobulin E (IgE) antibody, which recognizes FcepsilonRI-bound IgE and prevents binding of IgE to FcepsilonRI. In this study, we assessed the binding kinetics and affinity of monoclonal antibody 12 (mAb12) for IgE and investigated whether mAb12 can be used for depletion of IgE and isolation of IgE-bearing cells from peripheral blood.
Methods:  Binding kinetics and affinity for IgE were studied using Biacore surface plasmon resonance technique experiments. IgE antibodies were depleted from serum using sepharose-coupled mAb12 and IgE-bearing cells were enriched from heparinized blood samples with mAb12. The extent and biological relevance of IgE depletion were studied by quantitative IgE measurements and basophil histamine release experiments. Specific binding of mAb12 to IgE-bearing cells (basophils, mast cells, IgE-secreting plasma cells) was demonstrated by FACS.
Results:  Monoclonal antibody 12 shows rapid association (k_a = 5.46e5/Ms) with IgE, almost no dissociation (k_d = 8.8e−5/s) and an affinity for IgE (K_D = 1.61e−10 M), which is as high as that of FcepsilonRI. Immobilized mAb12 could be used to deplete IgE antibodies and isolate IgE-bearing cells from peripheral blood in a single-step procedure.
Conclusions:  Monoclonal antibody 12 is a high affinity anti-human IgE antibody, which efficiently removes IgE and IgE-bearing cells from peripheral blood and may thus be used for extracorporeal depletion of IgE and IgE-bearing cells.     

Sensitization to inhalant allergens between 4 and 8 years of age is a dynamic process: results from the BAMSE birth cohort

Background There is limited knowledge of the development of IgE-antibody levels over time in childhood, with respect to persistency and co-sensitization to specific inhalant allergens.
Methods Data from 2033 children participating in the BAMSE birth cohort was used. Background factors and clinical parameters were obtained and IgE antibody (ab) levels to eight common airborne allergens were measured (0.35 kU_A/L) when the children were 4 and 8 years of age.
Results Between 4 and 8 years the proportion of children sensitized to any of the inhalant allergens tested increased from 15% to 25%. At 4 years IgE-ab to birch and cat dominated, whereas at the age of 8, there was a considerable increase in the proportion of sensitization to timothy and dog. Except for mites and moulds, IgE-ab levels to all aeroallergens increased significantly between 4 and 8 years among those already sensitized at 4. Transient sensitization to inhalant allergen was uncommon. Furthermore, sensitization to birch pollen at 4 years increased the risk for becoming sensitized to timothy, cat and dog later in life. Such an association was not observed among those sensitized primarily to animal dander.
Conclusions There is a prominent process of sensitization at pre-school age to inhalant allergens, and in Northern Europe sensitization to birch pollen early in life seems to be important for this process. Such a process has a probable impact on the development of allergic disease in the growing child.     

After 6 years with Xolair; a 3-year withdrawal follow-up

Background:  This study reports the clinical and immunological state of patients 3 years after a 6-year period of Xolair treatment for severe allergic asthma.
Methods:  The patient's cat allergen sensitivity, measured as CD-sens, IgE and IgE- and IgG4 antibodies, was analysed and compared with asthma severity evaluated from FEV₁ and a questionnaire.
Results:  Three years after treatment with Xolair was stopped, 12/18 patients reported improved or unchanged asthma compared with ongoing Xolair treatment. Most of the patients were in a stable clinical condition, 16/18 had not increased nightly asthma attacks and 14/18 little or no increase in medication. The CD-sens to cat was still significantly lower ( P  < 0.02) than untreated patients with allergic asthma and lower than expected from their serum IgE antibody levels.
Conclusion:  Most of the patients in this study had, still 3 years after closing of 6 years Xolair treatment, a surprisingly mild and stable asthma. Interestingly, the observed, considerable, downregulation of basophil allergen sensitivity, CD-sens, most likely representing mast cell allergen sensitivity, contributed to the clinical results.     

Serum 25-hydroxyvitamin D and IgE – a significant but nonlinear relationship

Background:  Hormonal vitamin D system affects the determination of T-cell responses. It is unknown if there is an association between vitamin D status and allergic conditions. Our aim was to investigate differences in serum IgE concentrations by vitamin D status [measured by 25(OH)D] and by a genetic variation in a key vitamin D activation enzyme (CYP27B1) previously shown to be associated with type 1 diabetes.
Methods:  9377 participants in the 1958 British birth cohort completed a biomedical assessment at 45 years of age ; 7288 eligible participants had data on 25(OH)D and IgE, with 6429 having further information on CYP27B1 genotype (−1260C>A).
Results:  There was a nonlinear association between 25(OH)D and IgE ( P -value for curvature = 0.0001). Compared with the reference group with the lowest IgE concentrations [25(OH)D 100–125 nmol/l], IgE concentrations were 29% higher (95% CI 9–48%) for participants with the 25(OH)D <25 nmol/l, and 56% higher (95% CI 17–95%) for participants with 25(OH)D >135 nmol/l (adjusted for sex, month, smoking, alcohol consumption, time spent outside, geographical location, social class, PC/TV time, physical activity, body mass index and waist circumference). CYP27B1 genotype was associated with both 25(OH)D (difference for A vs. C allele: 1.88%, 95% CI 0.37–3.4%, P  = 0.01) and IgE concentrations (−6.59%, −11.6% to −1.42%, P  = 0.01).
Conclusions:  These data suggest that there may be a threshold effect with both low and high 25(OH)D levels associated with elevated IgE concentrations. The same CYP27B1 allele that is protective of diabetes was associated with increased IgE concentrations.     

Sensitivity and specificity of recombinant omega-5 gliadin-specific IgE measurement for the diagnosis of wheat-dependent exercise-induced anaphylaxis

Background:  A recent study has shown that the measurement of specific IgE antibodies to B-cell epitope peptides of wheat ω-5 gliadin (Pep A) and high molecular weight glutenin subunit (Pep B) are useful to diagnose wheat-dependent exercise-induced anaphylaxis (WDEIA).
Aims of the study:  We sought to compare the sensitivity and specificity of the in vitro tests for measuring the specific IgE antibodies to recombinant ω-5 gliadin (rω-5 gliadin) with those for wheat, gluten, Pep A, and Pep B in identification of patients with WDEIA.
Methods:  Fifty patients with WDEIA, 25 healthy subjects and 25 patients with atopic dermatitis with specific IgE antibodies to wheat but without experience of allergic reactions after ingestion of wheat products were enrolled in this study. The concentrations of specific IgE antibodies were measured using ImmunoCAP^TM. The empirical receiver operating characteristics curves (ROC) for each test were prepared and the areas under the ROC curve ( AUC ) were compared.
Results:  In patients with WDEIA, the sensitivities of the allergen-specific IgE tests for wheat, gluten, Pep A, Pep B and rω-5 gliadin were 48%, 56%, 76%, 22%, and 80%, respectively. The seven of 10 WDEIA patients with no specific IgE antibodies to rω-5 gliadin had specific IgE antibodies to Pep B. The highest AUC (0.850) was observed in the test for rω-5 gliadin.
Conclusions:  Measuring the concentration of specific IgE antibodies to rω-5 gliadin is more useful than to wheat, gluten, or Pep A in the identification of patients with WDEIA.     

The size of the disease relevant IgE antibody fraction in relation to 'total-IgE' predicts the efficacy of anti-IgE (Xolair®) treatment

Background:  Some patients with allergic asthma treated with anti-IgE (Xolair^®) do not become symptom free. Better criteria for response assessment than allergy skin tests or IgE determination are needed. The impact of the size of the disease relevant allergen-specific IgE antibody fraction, i.e. the percentage of IgE antibody of total IgE, was evaluated in cat allergic patients treated with the recommended doses of Xolair^®. Results were measured as changes in basophil allergen threshold sensitivity (CD-sens).
Methods:  In a double-blind placebo controlled trial 20 patients with a high (>3.8%) and 18 with a low (<1%) percentage of IgE antibodies to cat were given Xolair^® for 16 weeks and the change in CD-sens was compared to 11 and 10 patients, respectively, in each group receiving placebo.
Results:  The CD-sens dropped significantly in both the high ( P  < 0.001) and low ( P  < 0.001) group on Xolair^® but did not change significantly after placebo. For Xolair^®-treated patients, at the end of the trial there was a highly significant ( P  < 0.001) difference in CD-sens between the high group, where no patients, and the low group, where 13/18 patients, had become negative.
Conclusions:  The currently recommended doses of Xolair^® very efficiently eliminate IgE antibodies if the IgE antibody fraction is <1% of total IgE but has not enough effect on allergen sensitivity if the fraction is >3–4%. Further studies will show if increased doses of Xolair^® would help also these patients, who seem to represent about 1/3 of the patient population.     

Cat sensitization according to cat window of exposure in adult asthmatics

Background In adults, there is limited information on tolerance to cat, which may be reflected by high IgG₄ without IgE sensitization. Early exposure to cat may play a critical role.
Objective The aim was to assess among adults the association of Fel d 1 IgG₄, Fel d 1 IgE, skin prick test (SPT) response to cat and pet-related symptoms in relation to exposure to cat considering the period of exposure.
Methods SPT response to cat, specific IgE and IgG₄ to Fel d 1 were assessed in 167 asthmatics recruited in chest clinics (40 years of age in average) from the French Epidemiological study on the Genetics and Environment of Asthma (EGEA). Childhood and/or current exposure to cat were studied retrospectively.
Results IgG₄ was higher in relation to current cat exposure (0.53 vs. 0.09 ng/mL; P <0.001) and higher in women than in men. The period of cat exposure was significantly related to Fel d 1 IgE, the IgE/IgG₄ pattern and cat weal size. The lowest values of Fel d 1 IgE, cat weal size, pet-related nasal or respiratory symptoms were observed in those with both childhood and current exposure as well as the highest proportion of the IgE⁻/IgG₄⁺ pattern observed in 1.4%, 4.0%, 38.1% and 12.5% of those with −/−, +/−, +/+, −/+ childhood/current exposure, respectively.
Conclusions Adult asthmatics exposed to cats since childhood present an immunologic pattern with high IgG₄ and low IgE. Continuous exposure may maintain a state of immunological tolerance to cat.     

Variability of total serum immunoglobulin E levels from birth to the age of 10 years. A prospective evaluation in a large birth cohort (German Multicenter Allergy Study)

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.     

Neuropsychologic status at the age 4 years and atopy in a population-based birth cohort

Background:  Mental health has been reported to be associated with allergy, but only a few cohort studies have assessed if neurodevelopment predicts atopy.
Objective:  To investigate if neurobehavioral status of healthy 4-year-old children was associated with specific immunoglobulin E (IgE) at the same age and skin prick test results 2 years later.
Methods:  A population-based birth cohort enrolled 482 children, 422 of them (87%) provided neurobehavioral data, 341 (71%) had specific IgE measured at the age of 4 years; and 395 (82%) had skin prick tests completed at the age of 6 years. Atopy was defined as IgE levels higher than 0.35 kU/l to any of the three tested allergens at the age of 4 or as a positive skin prick test to any of the six tested allergens at the age of 6. McCarthy Scales of Child Abilities and California Preschool Social Competence Scale were the psychometric instruments used.
Results:  Twelve percent of children at the age of 4 and 17% at the age of 6 were atopic. Neurobehavioral scores were negatively associated with 6-year-old atopy after adjustment for socio-demographic and allergic factors, A relative risk of 3.06 (95% CI: 1.30–7.24) was associated with the lowest tertile (scorings ≤90 points) of the general cognitive scale. Similar results were found for verbal abilities, executive functions, and social competence. Asthma, wheezing, rhinitis, and eczema at the age of 6, but not at the age of 4, were associated with neurodevelopment at the age of 4.
Conclusions:  Neuropsychologic functioning and later atopy are negatively associated in preschool age children.     

A quantitative genetic analysis of intermediate asthma phenotypes

Aim:  To study the relative contribution of genetic and environmental factors to the correlation between exhaled nitric oxide (FeNO), airway responsiveness, airway obstruction, and serum total immunoglobulin E (IgE).
Methods:  Within a sampling frame of 21 162 twin subjects, 20–49 years of age, from the Danish Twin Registry, a total of 575 subjects (256 intact pairs and 63 single twins) who either themselves and/or their co-twins reported a history of asthma at a nationwide questionnaire survey, were clinically examined. Traits were measured using standard techniques. Latent factor models were fitted to the observed data using maximum likelihood methods.
Results:  Additive genetic factors explained 67% of the variation in FeNO, 43% in airway responsiveness, 22% in airway obstruction, and 81% in serum total IgE. In general, traits had genetically and environmentally distinct variance structures. The most substantial genetic similarity was observed between FeNO and serum total IgE, genetic correlation (ρ_A) = 0.37, whereas the strongest environmental resemblance was observed between airway responsiveness and airway obstruction, specific environmental correlation (ρ_E) = −0.46, and between FeNO and airway responsiveness, ρ_E = 0.34.
Conclusions:  Asthma is a complex disease characterized by a set of etiologically heterogeneous biomarkers, which likely constitute diverse targets of intervention.     

Development of allergy and IgE antibodies during the first five years of life in Estonian children

BACKGROUND: Epidemiological studies have demonstrated a low prevalence of allergic diseases and atopic sensitization among schoolchildren and young adults in the formerly socialist countries of Central and Eastern Europe as compared to Western Europe. OBJECTIVE: The aim of our study was to prospectively investigate IgE responses to food and inhalant allergens and the development of allergy during early childhood in a population with a low prevalence of atopic disorders. METHODS: In a population-based prospective study, 273 children were followed from birth through the first 5 years of life, recording manifestations of allergy by questionnaires and clinical examinations at 0.5, 1, 2 and 5 years (n = 213). Skin prick tests (SPT) were performed using natural foods (cow's milk, egg white) and commercial extracts of inhaled allergens (cat, dog, D. pteronyssinus, birch, timothy). In addition, serum IgE levels and circulating IgE antibodies against the seven allergens were determined. RESULTS: The prevalence of allergic diseases at 5 years of life was 19%. Atopic dermatitis was the most common allergic disease at all ages. The point prevalence of positive skin prick tests was 7% at 0.5, 1 and 2 years of age, and 3% at 5 years. Circulating IgE antibodies against food allergens were common at all ages, i.e. 13, 23, 36 and 36%, respectively, at 0.5, 1, 2 and 5 years. The prevalence of circulating IgE antibodies to inhalant allergens increased from 1.5% at 0.5 years to 11% at 1, 19% at 2 and 47% at 5 years. The antibody levels were generally low, however. The value of positive SPT and the presence of IgE antibodies in the diagnosis of clinical allergy were low. CONCLUSION: The results of this prospective study carried out in a previously socialist country with a low allergy prevalence among schoolchildren and young adults indicate that transient sensitization in early childhood is followed by a down-regulation of skin reactivity.     

ImmunoCAP Phadiatop Infant--a new blood test for detecting IgE sensitisation in children at 2 years of age

BACKGROUND: Correct diagnosis of immunoglobulin E (IgE)-mediated disease is the prerequisite for secondary allergy prevention during early childhood. OBJECTIVE: To evaluate the diagnostic efficacy of a new blood test, Phadiatop Infant, in detecting IgE sensitisation to food and inhalant allergens among children at 2 years of age. METHODS: Children (n = 239) were followed prospectively from birth to 2 years of age for the presence of IgE sensitisation and the development of atopic manifestations. Immunoglobulin E sensitisation was evaluated by skin prick test (SPT) and analysis of allergen-specific IgE antibodies in plasma to food and inhalant allergens. The children were classified into three groups: IgE-sensitised, non-IgE sensitised and inconclusive, depending on SPT and allergen-specific IgE results. RESULTS: Twenty-six (11%) of the children were classified as IgE-sensitised, 182 (76%) as non-IgE sensitised and 31 (13%) as inconclusive. Phadiatop Infant was positive in 50 (21%) of the children. Ten children (4%) with identified IgE antibodies against the selected food and inhalant allergens showed negative Phadiatop Infant. Three children showed positive Phadiatop Infant but were negative in the other tests performed. These results correspond to positive and negative predictive values for Phadiatop Infant of 89 and 99%, respectively. Children with clinical symptoms of atopic diseases had significantly increased levels for Phadiatop Infant (P < 0.01). CONCLUSION: Phadiatop Infant appears to be a reliable alternative to SPT and the measurement of allergen-specific IgE antibodies in plasma for detecting clinically important IgE sensitisation among children at 2 years of age.     

Influence of total serum IgE levels on the in vitro detection of β-lactams-specific IgE antibodies

Background Allergic reactions to β-lactams are a frequent cause of adverse drug reactions; the diagnosis is based on history, clinical examination, skin testing (prick and intradermal) and demonstration of serum-specific IgE antibodies (Abs).
Objective We compared the diagnostic performance of the Phadia CAP system for the detection of IgE to β-lactams carried out using the new test with cut-off limits of 0.10 kUA/L and the old test with cut-off limits of 0.35 kUA/L for positive results; subsequently, we analysed the effect of total serum IgE values and of atopic phenotype on the diagnostic performance of the tests.
Methods The study comprised a total of 34 patients with a history of immediate adverse reactions to β-lactams, which were confirmed by positive skin testing, and 115 control subjects with tolerance to β-lactams over the last year. The Phadia CAP System was used for the determination of serum total and specific IgE Abs towards penicilloyl G (c1), penicilloyl V (c2), ampicilloyl (c5) and amoxicilloyl (c6). The overall diagnostic performance was assessed as a diagnostic odds ratio (DOR).
Results The new test showed a higher sensitivity (85% vs. 44%) than the old test and a lower specificity (54% vs. 80%) but the overall diagnostic performance was poor (DOR 6.78 vs. 3.16, P =0.333) in both tests. The total IgE value influences the DOR of both tests; DOR was better for values under 200 kU/L [DOR=66; 95% confidence interval (CI): 11.3–384.1] or 500 kU/L (DOR=45.7; 95% CI: 5.3–394.4) for the new and old tests, respectively.
Conclusions The reduction in the positive cut off value has not significantly improved the overall diagnostic performance of the β-lactams-specific IgE assay. Because of the influence of serum total IgE on the detection of β-lactam-specific IgE Abs, the combination of both tests is mandatory in the in vitro diagnostic approach of β-lactam allergy.     

Genetic variation in CRTh2 influences development of allergic phenotypes

Background:  Allergic disorders are characterized by an increase in the Th2 cytokines IL-4, IL-5 and IL-13, produced primarily by Th2 cells. These cells are marked by the expression of CRTh2 ( c hemoattractant r eceptor-homologous molecule expressed on Th2 cells), a receptor for prostaglandin D₂. As genetic variation plays a significant role in the predisposition for allergic disorders, we investigated the influence of single nucleotide polymorphisms (SNPs) in CRTh2.
Methods:  In a large study population of German children ( n  = 4264) from the International Study of Asthma and Allergy in Children (ISAAC II), six polymorphisms in CRTh2 were genotyped. Statistical analyses were performed using single SNP and haplotype analyses.
Results:  Uncorrected associations among −6373G>A, +1431G>C and +1538A>G were observed with a number of allergic phenotypes ( P  < 0.05). After correction, association between +1431C and specific IgE to food allergens remained significant ( P  = 0.04). Associations of haplotype (H)3 (containing +1538G) with reduced risk for asthma and H2 (containing +1431C) with increased risk for specific IgE to food allergens also remained significant after correction for multiple testing ( P  = 0.004).
Conclusions:  Genetic variation within CRTh2 modifies the development of allergic sensitization and asthma in a population of German children.     

Primary versus secondary immunoglobulin E sensitization to soy and wheat in the Multi-Centre Allergy Study cohort

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.