Prediction of buckwheat allergy using specific IgE concentrations in children

INTRODUCTION: Buckwheat (BW) is considered to be one of the most important food allergens, and positive skin tests are found in about 5% of Koreans. We investigated the positive and negative predictive values of BW-specific IgE in subjects with a BW allergy in order to reduce the need for buckwheat challenge, which can be more riskier than other causes of food allergies. METHODS: Twenty-eight BW allergic subjects with symptoms after BW Open food challenge and 16 asymptomatic control subjects with positive skin test to BW were recruited. Serum samples from all patients were analyzed for BW-specific IgE antibodies using the Pharmacia CAP System. RESULTS: According to the receiver operator characteristic (ROC) analysis, the optimal cutoff level of BW-specific IgE, as the definitions of serum BW-specific IgE positive, was 1.26 kUA/l. With this selected cutoff level, the sensitivity, specificity, positive and negative predictive values were 93.10, 93.33, 79.75 and 97.96%, respectively. CONCLUSION: The use of the optimal cutoff level, 1.26 kUA/l, that simultaneously maximizes sensitivity and specificity, would be helpful for avoiding unnecessary risky challenge in children with a strong clinical history and skin test responses.     

Possible effect of landscape design on IgE recognition profiles of two generations revealed with micro‐arrayed allergens

The aim of this study was to investigate possible effects of landscape design on the IgE sensitization profile toward inhalant allergens in patients with respiratory allergy from Uzbekistan where green areas have been changed during the last two decades by a State program. Sera from two different generations of Uzbek (n=58) and, for control purposes, from two generations of Austrian (n=58) patients were analyzed for IgE reactivity to 112 different micro‐arrayed allergen molecules by ImmunoCAP ISAC technology. Changes in molecular IgE sensitization profiles to pollen allergens in the young vs the middle‐aged Uzbek population were associated with replanting, whereas those in the Vienna populations reflected natural changes in plant growth. Our data indicate that anthropologic as well as natural changes in the biome may have effects on IgE sensitization profiles already from one to another generation.     

Allergenic components of a novel food, Micronesian nut Nangai (Canarium indicum), shows IgE cross-reactivity in pollen allergic patients

BACKGROUND:New foods may present a risk for food hypersensitive patients. Several examples exist of allergic reactions caused by cross-reactive plant-derived foods, and new foods should be scrutinised before introducing them to the market. We have evaluated the clinical and serological relevance of cross-reactivity between Nangai and pollen allergens. METHODS: Cross-reactivity was examined with Maxisorp RAST (radioallergosorbent test), RAST inhibition and Western blot, using sera from patients allergic to grass, birch and mugwort pollen. None of the patients reported having seen or eaten Nangai previously. To determine the biological and clinical relevance of the cross-reactivity, histamine release (HR) test, skin prick test (SPT) and food challenge were used. RESULTS: There was prevalence for reactivity against Nangai in the group of pollen allergic patients. This cross-reactivity seems to be related--at least in part--to carbohydrate epitopes. Three out of 12 patients tested with Nangai were positive upon open challenge, but using double blind placebo controlled food challenge (DBPCFC) this could not be confirmed in two patients. The biological effects of Nangai on allergic patients were confirmed using HR and SPT. CONCLUSION: The Nangai specific IgE found among pollen allergic patients addresses the need for control of new or changed foods before introduction to the market.     

Quantitative analysis of IgE antibodies to food and inhalant allergens in 4-year-old children reflects their likelihood of allergic disease

BACKGROUND: It is well established that early diagnosis of allergic disease is warranted. METHODS: In a prospective birth cohort study (BAMSE) 3743 children at 4 years of age were included. Children were classified as having any allergic disease, e.g. asthma, suspected allergic rhinitis (suspAR), eczema or oro-gastro-intestinal symptoms with questionnaire. Blood was obtained from 2612 of these children and analysed for IgE antibodies (ab) towards 14 common food and airborne allergens. RESULTS: Positive IgE ab results were found in 38% of the children with any allergic disease, whereas such IgE ab results were found in 17% among those without any allergic disease. Furthermore, among children with any allergic disease the median summated IgE ab levels were 10.7 kU(A)/l compared with 1.5 kU(A)/l among those without such symptoms. The highest IgE ab levels were found to birch, peanut, cat and horse. When the sum of the IgE-ab levels towards the selected allergens was at least 34 kU(A)/l, or, alternatively, more than four allergen tests were positive, there was a 75% likelihood of identifying the individual with any allergic disease. To identify those with asthma, as well as those with suspAR, a significant interaction was found for the combination of the sum of IgE-ab levels and number of allergens positive at test. For eczema only, the number of positive allergens at test was associated to the likelihood of such disease. CONCLUSIONS: In children, 4 years of age, allergic disease was frequently not associated with the presence of single positive IgE antibody results, whereas increased IgE ab levels were significantly more prevalent among those with allergic disease. Thus, testing a certain profile of airborne and food allergens, and utilizing the sum of the IgE-ab levels in combination with the number of allergens positive at tests, may represent a more efficient diagnostic tool then to use just single positive IgE-ab results.     

Allergenic properties of kiwi-fruit extract: cross-reactivity between kiwi-fruit and birch-pollen allergens

Our investigation aimed to produce and characterize a kiwi extract and to use this extract to investigate a possible cross-reactivity with birch pollen. Kiwi was extracted in two buffers: phosphate-buffered saline (PBS) and borate-buffered saline (BBS). Extraction in BBS produced a double amount of protein, and a more stabile extract. Tandem crossed-immunoelectrophoresis showed that the BBS and PBS extracts had several common, but also a few individual, proteins. The mixture of both extracts was assumed to represent the most complete allergen extract. The allergenic properties of the kiwi extract were investigated by immunoblotting (IB), RAST, and histamine-release (HR) test in 15 birch-pollen-allergic patients (eight of them with clinical kiwi allergy) and one with clinical monoallergy to kiwi. All eight birch-pollen-allergic patients with kiwi allergy and the kiwi-monoallergic patient were positive in kiwi IB binding most frequently to proteins of 10-12 and 20-25 kDa. With our extract, RAST was positive in four kiwi-allergic and one non-kiwi-allergic patient, whereas the HR test was positive in five kiwi-allergic patients and negative in all non-kiwi-allergic patients. RAST and IB inhibition demonstrated cross-reactivity between birch-pollen and kiwi allergens due to a 10-12 kDa protein. In conclusion, a kiwi extract with allergenic properties was produced, and, by the methods used, cross-reactivity was demonstrated between birch-pollen and kiwi allergens.     

Diagnostic Decision Points of Specific IgE Concentrations in Korean Children With Egg and Cow's Milk Allergies

Purpose

The purpose of this study was to evaluate the utility of specific IgE (sIgE) concentrations for the diagnosis of immediate-type egg and cow''s milk (CM) allergies in Korean children and to determine the optimal cutoff levels.

Methods

In this prospective study, children ≥12 months of age with suspected egg or CM allergy were enrolled. Food allergy was diagnosed by an open oral food challenge (OFC) or through the presence of a convincing history after ingestion of egg or CM. The cutoff levels of sIgE for egg white (EW) and CM were determined by analyzing the receiver operating characteristic curves.

Results

Out of 273 children, 52 (19.0%) were confirmed to have egg allergy. CM allergy was found in 52 (23.1%) of 225 children. The EW-sIgE concentration indicating a positive predictive value (PPV) of >90% was 28.1 kU/L in children <24 months of age and 22.9 kU/L in those ≥24 months of age. For CM-sIgE, the concentration of 31.4 kU/L in children <24 months of age and 10.1 kU/L in those ≥24 months of age indicated a >90% PPV. EW-sIgE levels of 3.45 kU/L presented a negative predictive value (NPV) of 93.6% in children <24 months of age, while 1.80 kU/L in those ≥24 months of age presented a NPV of 99.2%. The CM-sIgE levels of 0.59 kU/L in children <24 months of age and 0.94 kU/L in those ≥24 months of age showed NPVs of 100% and 96.9%.

Conclusions

Our results indicate that different diagnostic decision points (DDPs) of sIgE levels should be used for the diagnosis of egg or CM allergy in Korean children. The data also suggest that DDPs with high PPV and high NPV are useful for determining whether OFC is required in children with suspected egg or CM allergy.     

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.     

Total serum IgE level influences oral food challenge tests for IgE‐mediated food allergies

Probability curves predicting oral food challenge test (OFC) results based on specific IgE levels are widely used to prevent serious allergic reactions. Although several confounding factors are known to affect probability curves, the main factors that affect OFC outcomes are currently unclear. We hypothesized that an increased total IgE level would reduce allergic reactivity. Medical records of 337 and 266 patients who underwent OFCs for 3.5 g boiled hen's egg white and 3.1 ml raw cow's milk, respectively, were examined retrospectively. We subdivided the patients into three groups based on total IgE levels and age by percentile (<25th, 25–75th, and >75th percentiles), and logistic regression analyses were performed on each group. Patients with higher total IgE levels were significantly less responsive. In addition, age did not significantly affect the OFC results. Therefore, total IgE levels should be taken into account when predicting OFC results based on food‐specific IgE levels.     

Sensitivity and specificity of specific IgE,skin prick test and atopy patch test in examination of food allergy

The aim of this study is the evaluation of the specificity and sensitivity of the skin prick tests (SPTs), specific IgE and atopy patch tests (APTs) in atopic dermatitis patients suffering from food allergy. A total of 301 patients were examined, complete dermatological and allergological examination was performed in all patients. The food allergy was confirmed to peanuts in 62 patients (20%), to egg in 16 patients (5%), to soy in 9 patients (3%), to wheat in 12 patients (4%) and to cow milk in 6 patients (2%). The specificity of SPT, specific IgE and APT is considered as good; the sensitivity of APT is low. The positive results in isolation cannot confirm the food allergy; however, together with other diagnostic methods, such as clinical history and open exposure test, these tests are valuable tool in examination of food allergy.     

Association of interleukin 18 (IL18) polymorphisms with specific IgE levels to mite allergens among asthmatic patients

BACKGROUND: Allergy is regarded as a multifactorial condition. Its onset and severity are influenced by both genetic and environmental factors. Identification of genetic factors involved in asthma development and related phenotypes is a major task in understanding the genetic background of asthma. The possible involvement of IL18 polymorphisms in asthma was examined in a Korean asthma cohort. METHODS: Direct sequencing was performed to discover single-nucleotide polymorphisms (SNPs) in the IL18 gene. Single-base extension (SBE) method was employed for genotyping. Genotypic influence of IL18 was analysed using logistic and multiple-regression models. RESULTS: Although no polymorphisms in the IL18 gene showed significant association with the risk of asthma development, analyses of the association with specific serum IgE levels to Dermatophagoides farinae (D.f.) and D. pteronyssinus (D.p.) among asthmatic patients revealed significant associations with two completely linked SNPs, i.e. -148G>C and +13925A>C(Ser35Ser) (P = 0.01-0.11 for D.f. and P = 0.005-0.11 for D.p.). Both C allele of -148G>C and C allele of +13925A>C showed gene dose-dependent effects on the levels of specific IgE. The lowest IgE levels in homozygotes of minor alleles (1.13 and 1.22 of D.f.; 1.38 and 1.33 of D.p., respectively), intermediate IgE levels in heterozygotes (1.60 and 1.70 of D.f.; 1.84 and 1.92 of D.p., respectively), and the highest levels in homozygotes for major allele (1.93 and 1.93 of D.f.; 2.24 and 2.24 of D.p., respectively), were found. CONCLUSION: The genetic relevance of IL18 to specific IgE might offer an important step in understanding the genetic background of allergic diseases.     

Similar localization of conformational IgE epitopes on the house dust mite allergens Der p 5 and Der p 21 despite limited IgE cross‐reactivity

Background

Due to high IgE recognition frequency and high allergenic activity, Der p 5 and Der p 21 are clinically important house dust mite (HDM) allergens. The objective of this study was to characterize the immunodominant IgE epitopes of Der p 5 and Der p 21 responsible for their high allergenic activity.

Methods

A panel of 12 overlapping peptides spanning the Der p 5 and Der p 21 sequence were synthesized to search for sequential IgE epitopes by direct testing for allergic patients' IgE reactivity. Peptide‐specific antibodies raised in rabbits were used in inhibition studies for localizing conformational IgE epitopes which were visualized on the surfaces of the allergen structures by molecular modelling. IgE cross‐reactivity between the allergens was investigated by IgE inhibition studies.

Results

Immunodominant IgE epitopes defined by allergic patients' IgE on Der p 5 and Der p 21 were primarily of the conformational, discontinuous type including N‐ and C‐terminal portions of the protein. They could be located on each allergen on one area with similar localization, but despite similar structure of the allergens, no relevant IgE cross‐reactivity could be detected.

Conclusion

Our study shows that Der p 5 and Der p 21 contain a major conformational IgE epitope‐containing area located on similar portions of their structure, but they lack relevant IgE cross‐reactivity. These data are important for the development of modern allergy vaccines based on defined molecules for allergen‐specific immunotherapy of HDM allergy.     

Comparison between two automated systems to determine specific IgE: CAP and ELItest

Background and objective The ELItest® is a newly developed system to measure specific IgE based on allergen bound to paper rings and an alkaline phosphatase conjugated second antibody detection system. It was compared to the CAP® system, a method based on allergen conjugated to an encapsulated cellulose polymer and a β-galactosidase conjugated fluorescence detection system. Methods Sera of 300 patients with positive history and positive skin-prick tests to common allergens (birch, timothy-grass, cat dander, dermatophagoides pteronyssinus, wasp venom) and 30 negative controls were tested in both systems. Serial dilutions of high titre sera were measured; inter- and intraassay coefficients of variation (cv) were determined. Results The CAP system proved to be more sensitive (92.3%) compared to ELItest (84%) but marginally less specific (94.7% for CAP versus 96.7% for ELItest). Intraassay cv were slightly lower in the ELItest (7.2% CAP versus 6.4% ELItest), whereas the interassay cv was roughly twice as high for ELItest (20.1%) than for the CAP system (11.4%). Linearity over an 8-fold dilution was good in both tests (r² 0.979 ELItest versus 0.996 CAP), although ELItest levelled off at higher allergen concentrations. Similarly, correlation analysis between both systems revealed that ELItest consistently measured lower values, especially at higher concentrations of specific IgE. The slope of the linear regression line of a log/log plot of measured IgE concentrations was significantly lower than 1 in birch, cat and wasp; the y-intersect was significantly lower than 0 in all analysed allergens. Conclusion These results suggest that the ELItest system for the measurement of specific IgE is not quite as reproducible and sensitive as the CAP system but slightly more specific, and that higher concentrations of specific IgE are measured lower in the ELItest. One potential reason might be that the amount of allergen bound to a paper ring might be smaller than that bound to a cellulose polymer, but further experiments are necessary to prove this hypothesis.