Prenatal prediction of infant atopy by maternal but not paternal total IgE levels

BACKGROUND: The atopic history of parents has long been used to predict infant atopy. However, bias from questionnaires of allergic history are also frequently suspected, because a large number of vasomotor rhinitis, intrinsic asthma, and seborrheic dermatitis cases are probably misinterpreted to be atopic diseases. OBJECTIVE: We attempted to identify a risk factor other than parental atopic history to predict elevated infant IgE levels and infant atopy. METHODS: A total of 655 core families were prenatally recruited, and finally 545 families completed the study for the prospective analysis of infant atopy at 6 months of age. Atopic history and blood samples of parents were collected in the third trimester during pregnancy. Cord blood (CB) was collected immediately after birth. Infant blood samples and history of infant eczema were collected in the 6-month physical checkup clinic. Blood total IgE and specific IgE levels were determined by use of the Pharmacia CAP system. RESULTS: In univariate analysis, maternal, but not paternal, atopic history correlated with elevated CB IgE levels and the occurrence of infant eczema. Elevated maternal, but not paternal, total IgE levels (>150 KU/L) significantly correlated with increases of CB IgE levels (median, 0.54 vs 0.17 KU/L, P <.001), infant IgE levels (log-transformed mean values, 1.32 +/- 0.51 vs 1.13 +/- 0.51 KU/L, P <.001), and infant eczema (P =.008). Multivariate logistical regression analysis, however, showed that only maternal total IgE levels correlated with CB and infant IgE levels and the development of infant eczema. CONCLUSIONS: The maternal, but not paternal, total IgE level correlates with elevated infant IgE levels and infant atopy. This provides a high specificity (83%) and a sensitivity of 34% for prediction of infant atopy. This suggests that maternal factors, placental factors, or both have an impact on perinatal allergic sensitization.     

A method for the simultaneous determination of serum and cell-bound IgE

A method for determining the amount of total IgE bound to leucocytes has been devised by measuring that released on incubating various cell number dilutions in acetate buffer pH 4.0. A linear relationship between IgE released and cell number was obtained over a limited concentration range. The method seemed to work satisfactorily with 50 ml of whole blood for those subjects with very high serum levels of total IgE. However, with subjects having a slightly elevated or normal serum IgE level it may be necessary to use twice the amount of blood.     

Association of IL13 with total IgE: evidence against an inverse association of atopy and diabetes

BACKGROUND: Atopic illnesses, related to high circulating IgE levels, and the autoimmune disease type 1 diabetes, have been reported to be inversely associated. One possible explanation is that susceptibility alleles for one disease provide protection for the other. OBJECTIVE: Using the largest sample sizes reported so far for the identification of genetic determinants of circulating IgE levels, we investigated associations between total serum IgE (log-transformed) and single nucleotide polymorphisms in 8 genes that are candidate susceptibility loci for IgE levels/atopic illness (IL13, IL4, IL4RA, FCER1B, IL12B, TBET) and/or type 1 diabetes (CTLA4, PTPN22, IL2RA). METHODS: As many as 4570 DNA samples obtained from members of the British 1958 Birth Cohort were genotyped for 51 candidate variants, and the associations of alleles and genotypes with log-transformed serum IgE levels were evaluated by regression modeling. RESULTS: We obtained evidence of association between IL13 variants and total serum IgE levels (P = .00002, explaining 0.59% of phenotypic variance). However, there was no evidence of association of the confirmed type 1 diabetes susceptibility genes CTLA4 and PTPN22 and the candidate gene IL2RA with IgE levels. CONCLUSION: Allelic variation in the IL-13 gene is robustly confirmed as a contributor to the variance of IgE levels but has no detectable effect in type 1 diabetes. CLINICAL IMPLICATIONS: Although the allelic variation at the confirmed IL-13 locus explains too little of the between-individual variation of circulating IgE to be of use for clinical prediction on its own, the discovery of additional susceptibility loci in the future may aid in the stratification of atopic subjects and improve risk assessment.     

A simple method for the measurement of low levels of serum IgE

A simple method for the estimation of low serum IgE levels is presented. Radioimmunoassay often gives falsely high values because of the presence of non-specific factors in the serum when an excessive amount of serum is used in order to measure low serum IgE levels. Therefore the serum sample has to be diluted to minimize the influence of the non-specific factors and the lowest IgE level measurable in the serum is about 5 u/ml. In this study, pretreatment of the serum with cellulose powder was found to remove the non-specific factors that yield falsely high values. These factors were adsorbed almost completely onto cellulose powder when the serum IgE level was less than 100 u/ml. Thus, low serum IgE levels could be determined by radioimmunoassay using a sufficient amount of serum pretreated by cellulose powder. The lowest serum IgE level measurable by this method was as low as 0.5 u/ml and the low IgE level in neonatal serum could be determined with sufficient accuracy. By this method the geometric level of IgE in cord serum was 2.45 u/ml with a ±2 standard deviations range of 1.04 to 5.80 u/ml.     

Multidisc RAST: a reliable method for screening of specific IgE antibodies in serum?

"Multidiscs" (md) are cellulose discs to which several allergens are coupled, allowing the simultaneous screening of several specific IgE antibodies. We compared RAST performed with md to RAST performed with the corresponding individual allergens coated on single discs (sd). One hundred and twenty-two RAST positive samples were analyzed for four different allergen groups: moulds, cereals, weed pollens and tree pollens. We found lower RAST sensitivity when screening with mds than with the individual sds in all allergen groups except cereals. In 30 to 70% of the samples, the results were concordant. In 25.5 to 66.7%, md values were lower and in 1.3 to 26.3% higher than sd values. When only qualitative results were considered, the loss of sensitivity appeared acceptable: only 6.7 to 16.7% of the sd positive samples were not detected by md screening. A cost-benefit analysis, calculated on local data, confirmed economic advantages.     

An ELISA-based method for measurement of food-specific IgE antibody in mouse serum: an alternative to the passive cutaneous anaphylaxis assay

Passive cutaneous anaphylaxis (PCA) assay has been a gold standard method to measure allergen-specific IgE antibody (ASIgE Ab) levels in allergy mouse models. Many factors including stringent guidelines for laboratory animal use make PCA a difficult choice. Therefore, alternative methods are needed that can be readily applied for measurement of specific IgE antibody levels in mouse serum. Herein we describe a novel ELISA-based method that is more sensitive in comparison to PCA, IgE isotype-specific (because it has little cross-reactivity with IgG1 or IgG2a isotype) and highly reproducible (<10% inter- or intra-assay variation). Furthermore, we demonstrate the utility of this assay to measure specific IgE Ab against a variety of food extracts including chicken egg, peanut, almond, filbert/hazelnut and sweet potato. These findings are of particular interest to those who are seeking (i) to measure food-extract-specific IgE antibody in animal models and (ii) an alternative to the animal-based PCA method to measure mouse IgE antibodies.     

Cord blood IgE: its determinants and prediction of development of asthma and other allergic disorders at 12 months.

BACKGROUND: The value of cord blood IgE in predicting the development of asthma and other IgE-mediated allergic diseases is unclear. OBJECTIVE: The purpose of this study is twofold: (1) to determine factors affecting cord blood IgE level and (2) to determine whether cord blood IgE predicts the development of asthma and other IgE-mediated allergic diseases in high risk (defined as those with at least one first degree relative with asthma or 2 first degree relatives with other IgE-mediated allergic diseases) infants at 12 months. METHODS: The study utilized cord blood obtained from a group of high risk infants who took part in a randomized controlled trial to assess the effectiveness of an intervention program in the primary prevention of asthma and other IgE-mediated allergic diseases. Total IgE and cotinine in the cord blood were measured. Assessment of the infants was done at 12 months for these diseases. RESULTS: Sixty-four (17.8%) infants had detectable total IgE in cord blood >0.5 kU/L. The proportion of infants with elevated cord blood IgE was significantly higher among nonwhites, birth during winter months, and those with a maternal history of asthma. There was no correlation between cord blood IgE and cord blood cotinine level. Cord blood IgE was found to be a significant predictor for the development of urticaria due to food allergy but not for other outcomes. CONCLUSION: Both genetic and environmental risk factors play a role in determining the level of IgE in cord blood. Cord blood IgE was a significant risk factor for the development of urticaria due to food allergy at 12 months of life. As urticaria due to food allergy is a prodrome for anaphylaxis, measurement of IgE in cord blood may be indicated in infants at high risk for developing allergic diseases so that preventive measures can be applied.     

Cord and blood levels of newborn IgE: Correlation,role and influence of maternal IgE

The role of cord blood immunoglobulin E (IgE) levels in predicting the development of atopy has been widely investigated. The aim of the study was to evaluate the correlation between serum and cord blood total IgE in newborns and the possible influence of the atopic status of the mother on them. It was also investigated the possible role of gestational age on neonatal total IgE levels. We considered 763 deliveries, 724 ≥ 37 weeks of gestation and 39 < 37 weeks of gestation. 14% of mothers (13.7% at term, 15.4% preterm) showed high total IgE levels. The results showed a significant correlation between serum and cord IgE levels both in preterm and term newborns. The data revealed also that mother’s total IgE levels affect both neonatal serum and cord total IgE levels. For the latters we also found child gender as an additional independent predictor. On the contrary total IgE levels are not affected by gestational age. Clinical limitations of total IgE is known but their determination can be useful to define atopy and to suggest follow-up of the children.     

Cord blood IgE. III. Prediction of IgE high-response and allergy

Screening of total IgE in 2814 cord blood samples was analysed by Phadebas IgE PRIST in 2 1-year birth cohorts (1983–1984 and 1985–1986) in Denmark (n= 1189 + 1625). For follow-up we chose all infants with cord blood IgE≥0.5 kU/1 and a randomly chosen group of the same size with cord blood IgE < 0.5 kU/1. A total group of 762 infants were clinically evaluated at 18 months of age, and in 688 of these we evaluated total and specific IgE. A diagnosis of definite atopy, probable atopy or no atopy was established. In the present study we defined allergic disease as atopic disease combined with elevated total IgE. We found a statistically significant correlation between cord blood IgE and IgE at 18 months of age. Significantly more infants with elevated cord blood IgE had developed allergic disease at 18 months. A cut-off value of 0.3 kU/1 for cord blood IgE was superior to the originally suggested 0.5 kU/1. Significantly more infants with elevated cord blood IgE had developed specific IgE antibodies at 18 months. The most frequent specific IgE antibody was towards cow's milk. Specific IgE antibodies were very rarely found when total IgE was not elevated. A total IgE at the age of 18 months > 26 kU/1 could be regarded as elevated. With regard to allergic disease the positive predictive values of cord blood lgE≥0.3 kU/1 in the 2 series were 21 % and the corresponding sensitivities 67% and 46%, respectively. The risk of developing allergic disease was elevated with a factor 3 to 4 when cord blood IgE ≥ 0.3 kU/1. In a high-risk group based on atopic predisposition and elevated eord blood IgE ≥0.5 kU/1 the relative risk of allergic disease was 5, the predictive value of positive test 38%, the sensitivity 24% and the specificity 96%. Clinical aspects Cord blood IgE was a good predictor of allergic disease at the age of 18 months. A cord blood cut-off IgE value of 0.3 kU/l was superior to other cord blood IgE values with the Phadebas IgE PRIST method.     

Predictors of cord blood IgE levels in children at risk for asthma and atopy

BACKGROUND: Increased cord blood IgE levels, in conjunction with a family history of atopy, are associated with the development of allergic diseases in children. However, little is known about predictors of cord blood IgE levels. OBJECTIVE: Our objective was to identify predictors of cord blood IgE levels among infants at increased risk of atopy. METHODS: Cord blood IgE levels were measured in 874 infants who were screened for participation in a birth cohort. Questionnaires were administered after birth of the infant, and maternal and cord blood was obtained for measurement of IgE levels. Logistic and tobit regression models were used to study the association between perinatal factors and cord blood IgE levels. RESULTS: In multivariable models infant male sex, increased maternal total IgE level, maternal allergen sensitization, Hispanic ethnicity, and residence in low-income areas were associated with detectable or increased cord blood IgE levels, whereas increasing maternal age was associated with undetectable or lower cord blood IgE levels. Although maternal smoking during pregnancy was positively associated with cord blood IgE levels in univariable models, the effect did not persist after adjusting for potential confounders. CONCLUSION: Maternal allergen sensitization, markers of socioeconomic disadvantage and race/ethnicity, maternal age, and infant sex might influence fetal production of IgE. We found no association of maternal parity, mode of delivery, gestational age, or season of birth with cord blood IgE levels. CLINICAL IMPLICATIONS: The identification of these definable familial and environmental factors that predict cord blood IgE levels might help in the early detection of infants at risk for atopic disorders.     

Determinants of bronchial responsiveness in the European Community Respiratory Health Survey in Italy: evidence of an independent role of atopy, total serum IgE levels, and asthma symptoms

The aim of the analysis was to test whether total serum IgE levels, specific serum IgE levels, and asthma symptoms are independent predictors of bronchial hyperresponsiveness (BHR), after controlling for known risk factors or potential confounders. The study was carried out on a sample of 875 young adults, 20–44 years old, who took part in the European Community Respiratory Health Survey in Italy The subjects underwent a dose-response methacholine challenge test. We also measured airway caliber as the baseline FEV, in absolute terms and as percentage of forced vital capacity (FVC); skin wheal response to 11 common environmental allergens; and total and specific serum IgE levels to mites, molds, pets, and respiratory symptoms by means of a standardized questionnaire. Atopy (positive skin prick test and/or positive specific IgE assay), total IgE, asthma symptoms, airway caliher, and age appeared to be independent predictors of BHR. When all the other risk factors were taken into account, atopy and total IgE were associated with a threefold increase in BHR risk and thus emerged as the main determinants of BHR. The importance of symptom status as a determinant of BHR decreased remarkably after controlling for atopy and IgE: the odds ratio of current asthmatics to asymptomatic subjects decreased from 15.3 to 8.8. When controlling for symptoms and atopy, a family history of allergic diseases and early respiratory infections was not found to be associated with BHR. Both FEVi and FEV/FVC were strongly and inversely associated with BHR. When airway caliher was taken into account, older age was associated with decreased responsiveness, and the level of responsiveness did not differ significantly between males and females and between smokers and nonsmokers. The results from this analysis indicate that at any given age, irrespective of sex and smoking habits, total serum IgE, specific IgE, airway caliber, and asthma symptoms are the main independent factors influencing the occurrence of BHR in a young adult sample.     

Cord serum IgE in relation to family history and as predictor of atopic disease in early infancy

Cord serum IgE was assayed by particle counting immunoassay (PACIA) in an unselected series of European newborns (n = 190; geom mean = 0.37 IU/ml) and a cutoff limit established (≥ 1.20 IU/ml) for prediction of atopy. At control follow-up by questionnaire 18 months after birth, 38 infants (20.0%) had developed definite (9.5%) or probable (10.5%) atopy with a significant predominance of boys ( P < 0.03). Infants with a positive immediate family history (IFH) had a higher risk of developing atopy ( P < 0.0025) and also had a higher incidence of elevated cord IgE ( P < 0.02) than infants with a negative IFH. Maternal atopy influenced cord IgE levels significantly ( P < 0.00005), whereas paternal atopy did not ( P = 0.23). No fetal IgE antibodies against five common allergens could be demonstrated in 36 cord sera tested. Breast-feeding for 3 months was not sufficient to prevent atopic symptoms. The predictive value of cord IgE was high since 26 of 36 newborns (positive predictive value = 72.2 %) with elevated cord IgE had developed atopic symptoms before follow-up. Of the 38 infants who developed atopic symptoms, 26 had elevated cord IgE (sensitivity = 68.4%) compared to only 10 (6.6%) of the 152 atopy-free infants (P < 0.00005). The data indicate that elevated cord IgE as determined by PACIA is a good predictor of early-onset atopy, better than family history ( P < 0.008), and that primarily maternal atopy seems to affect fetal IgE synthesis.     

Predictors of Atopic Disease: Cord Blood IgE and Month of Birth

The cumulated incidence of atopic disease before 7 years of age was highly influenced by the cord blood IgE concentration and moderately influenced by the month of birth: obvious atopic disease was more than twice as common in children with high cord blood IgE and born in May than in children with a similar IgE and born in November (P less than 0.05). There was no similarly increased risk for atopic disease among those born in May with low cord blood IgE. Environmental factors thus seem important merely for a high risk population. The findings lend support to family planning when there is especially high genetic risk for atopic disease.