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1.  IgE but not IgG4 Antibodies to Ara h 2 Distinguish Peanut Allergy from Asymptomatic Peanut Sensitization 
Allergy  2012;67(12):1538-1546.
Background
There are no available clinical tests that can accurately predict peanut allergy (PA) and/or anaphylaxis. This study is aimed at evaluating whether the component-resolved diagnostic (CRD) IgE and IgG4 tests can 1) distinguish PA from asymptomatic peanut sensitization; and 2) differentiate anaphylactic vs. non-anaphylactic PA.
Methods
This study included 20 non-atopic controls, 58 asymptomatically peanut-sensitized children, 55 non-anaphylactic and 53 anaphylactic PA cases from the Chicago Food Allergy Study. IgE and IgG4 to 103 allergens were measured using the ImmunoCAP ISAC technology, and were compared among each group of children. The random forest test was applied to estimate each allergen’s ability to predict PA and/or peanut anaphylaxis.
Results
PA cases (with or without anaphylaxis) had significantly higher IgE reactivity to Ara h 1–3 (peanut allergens) and Gly m 5–6 (soy allergens) than asymptomatically-sensitized children (p<0.00001). Similar but more modest relationships were found for IgG4 to Ara h 2 (p<0.01). IgE to Ara h 2 was the major contributor to accurate discrimination between PA and asymptomatic sensitization. With an optimal cutoff point of 0.65 ISU-E, it conferred 99.1% sensitivity, 98.3% specificity, and a 1.2% misclassification rate in the prediction of PA, which represented a higher discriminative accuracy than IgE to whole peanut extract (p=0.008). However, none of the IgE and/or IgG4 tests could significantly differentiate peanut anaphylaxis from non-anaphylactic PA.
Conclusions
IgE to Ara h 2 can efficiently differentiate clinical PA from asymptomatic peanut sensitization, which may represent a major step forward in the diagnosis of PA.
doi:10.1111/all.12047
PMCID: PMC3499645  PMID: 23094689
Ara h 2; Component-resolved diagnostics; Diagnostic performance; Peanut allergy; Peanut anaphylaxis
2.  Gene Polymorphisms, Breastfeeding and Development of Food Sensitization in Early Childhood 
Background
The impact of breastfeeding on the development of allergic disease is uncertain. There are no data that show whether this relationship varies by individual genotypes.
Objective
To evaluate the effect of breastfeeding and gene-breastfeeding interactions on food sensitization (FS) in a prospective U.S. birth cohort.
Methods
This study included 970 children who were prospectively followed since birth. Breastfeeding history was obtained from a standardized questionnaire interview. FS was defined as specific IgE ≥0.35 kUA/L to any of eight common food allergens. Eighty-eight potentially functional SNPs were genotyped from 18 genes involved in innate immunity or TH1/TH2 balance. Logistic regression models were used to test the effects of breastfeeding and gene-breastfeeding interactions on FS, with adjustment for pertinent covariates.
Results
Children who were ever breastfed (n=739), including exclusively breastfed children, were at a 1.5 (95%CI=1.1-2.1, p=0.019) times higher risk of FS than never breastfed children (n=231). This association was significantly modified by rs425648 in the IL12RB1gene (pinteraction=0.0007): breastfeeding increased the risk of FS (OR=2.0, 95%CI=1.4-3.1, p= 0.0005) in children carrying the GG genotype but decreased the risk (OR=0.6, 95%CI=0.3-1.4, p=0.252) in children carrying the GT/TT genotype. Similar interactions were observed for SNPs in the TLR9 (rs352140) and TSLP (rs3806933) genes. The interaction between the combined genotypes of the three SNPs and breastfeeding on FS was even stronger (pinteraction<10-5).
Conclusion
Our data suggest that the effect of breastfeeding on FS was modified by SNPs in the IL12RB1, TLR9, and TSLP genes both individually and jointly. Our findings underscore the importance of considering individual genetic variations in assessing this relationship.
doi:10.1016/j.jaci.2011.05.007
PMCID: PMC3149737  PMID: 21689850
Breastfeeding; food sensitization; gene-environment interaction
3.  Early Life Eczema, Food Introduction, and Risk of Food Allergy in Children 
The effect of food introduction timing on the development of food allergy remains controversial. We sought to examine whether the presence of childhood eczema changes the relationship between timing of food introduction and food allergy. The analysis includes 960 children recruited as part of a family-based food allergy cohort. Food allergy was determined by objective symptoms developing within 2 hours of ingestion, corroborated by skin prick testing/specific IgE. Physician diagnosis of eczema and timing of formula and solid food introduction were obtained by standardized interview. Cox Regression analysis provided hazard ratios for the development of food allergy for the same subgroups. Logistic regression models estimated the association of eczema and formula/food introduction with the risk of food allergy, individually and jointly. Of the 960 children, 411 (42.8%) were allergic to 1 or more foods and 391 (40.7%) had eczema. Children with eczema had a 8.4-fold higher risk of food allergy (OR, 95% CI: 8.4, 5.9–12.1). Among all children, later (>6 months) formula and rice/wheat cereal introduction lowered the risk of food allergy. In joint analysis, children without eczema who had later formula (OR, 95% CI: 0.5, 0.3–0.9) and later (>1 year) solid food (OR, 95% CI: 0.5, 0.3–0.95) introduction had a lower risk of food allergy. Among children with eczema, timing of food or formula introduction did not modify the risk of developing food allergy. Later food introduction was protective for food allergy in children without eczema but did not alter the risk of developing food allergy in children with eczema.
doi:10.1089/ped.2010.0014
PMCID: PMC3281290  PMID: 22375277
4.  Familial Aggregation of Food Allergy and Sensitization to Food Allergens: A Family-Based Study 
Summary
Background
The increasing prevalence of food allergy (FA) is a growing clinical and public health problem. The contribution of genetic factors to FA remains largely unknown.
Objective
This study examined the pattern of familial aggregation and the degree to which genetic factors contribute to FA and sensitization to food allergens.
Methods
This study included 581 nuclear families (2,004 subjects) as part of an ongoing FA study in Chicago, IL, USA. FA was defined by a set of criteria including timing, clinical symptoms obtained via standardized questionnaire interview, and corroborative specific IgE cutoffs for >=95% positive predictive value (PPV) for food allergens measured by Phadia ImmunoCAP. Familial aggregation of FA as well as sensitization to food allergens were examined using generalized estimating equation (GEE) models, with adjustment for important covariates including age, gender, ethnicity and birth order. Heritability was estimated for food-specific IgE measurements.
Results
FA in the index child was a significant and independent predictor of FA in other siblings (OR=2.6, 95%CI:1.2–5.6, p=0.01). There were significant and positive associations among family members (father-offspring, mother-offspring, index-other siblings) for total IgE and specific IgE to all the 9 major food allergens tested in this sample (sesame, peanut, wheat, milk, egg white, soy, walnut, shrimp and cod fish). The estimated heritability of food-specific IgE ranged from 0.15 to 0.35 and was statistically significant for all the 9 tested food allergens.
Conclusion
This family-based study demonstrates strong familial aggregation of food allergy and sensitization to food allergens, especially, among siblings. The heritability estimates indicate that food-specific IgE is likely influenced by both genetic and environmental factors. Together, this study provides strong evidence that both host genetic susceptibilityand environmental factors determine the complex trait of IgE-mediated food allergy.
doi:10.1111/j.1365-2222.2008.03111.x
PMCID: PMC2729087  PMID: 19016802
familial aggregation; heritability; food allergy; sensitization to food allergens; IgE-mediated
5.  Dissociation between the Prevalence of Atopy and Allergic Disease in Rural China among Children and Adults 
Background
The prevalence of allergic diseases is increasing worldwide, but the reasons are not well understood. Previous studies suggest that this trend may be associated with lifestyle and urbanization.
Objective
To describe patterns of sensitization and allergic disease in an unselected agricultural Chinese population.
Methods
The data was derived from a community-based twin study in Anqing, China. Skin prick testing was performed to foods and aeroallergens. Atopy was defined as sensitization to ≥1 allergen. Allergic disease was ascertained by self-report. The analysis was stratified by sex and age (children [11-17 years] and adults [≥18 years]) and included 1059 same-sex twin pairs.
Results
Of 2118 subjects, 57.6% were male (n=1220). Ages ranged from 11-71 years; 43.3% were children (n=918). Atopy was observed in 47.2% (n=999) of participants. The most common sensitizing foods were shellfish (16.7%) and peanut (12.3%). The most common sensitizing aeroallergens were dust mite (30.6%) and cockroach (25.2%). Birth order and zygosity had no effect on sensitization rates. Multivariate logistic regression models revealed risk factors for sensitization include age for foods and sex for aeroallergens. The rates of food allergy and asthma were estimated to be <1%.
Conclusions
Atopic sensitization was common in this rural farming Chinese population, particularly to shellfish, peanut, dust mite, and cockroach. The prevalence of allergic disease, in contrast, was quite low.
Clinical Implications
Allergen sensitization was far more common than the rate of self-reported allergic disease in this community. Evidence of sensitization is an inadequate marker of allergic disease and better correlates with clinical disease are needed.
Capsule summary
Among this large unselected Chinese rural farming community, atopy was observed in nearly half of the study subjects, but the rate of allergic disease was comparatively very low.
doi:10.1016/j.jaci.2008.08.009
PMCID: PMC2747487  PMID: 18805578
aeroallergens; rural; farming community; Chinese; food allergens; prevalence; sensitization; skin prick tests

Results 1-5 (5)