High anti-IgE levels at birth are associated with a reduced allergy prevalence in infants at risk: a prospective study

Development of atopic disease was prospectively studied in 148 children from birth to the age of 18 months and related to serum levels of IgG anti-IgE antibody. Children with a dual heredity of allergy, but remaining healthy, had significantly higher IgG anti-IgE levels at birth than children with a similar predisposition to allergy, who became allergic. Children with increased allergy risk, defined by elevated IgE levels at birth (>= 0.53 kU/l) and with probable allergy symptoms had also significantly higher IgG anti-IgE levels at birth than children of the same risk group, developing definite allergy. Independent of allergy risk, there was a significantly lower prevalence of atopic disease in children with cord serum levels of IgG anti-IgE above 350AU.1 than in children with lower levels. Additionally, we showed that the allergy predictive capacity of IgE levels in cord serum was slightly improved in specificity, sensitivity and efficiency by including not only the family history of allergy, but also cord serum levels of IgG anti-IgE. Our results thus raise the possibility that high levels of IgG anti-IgE protect children of increased allergy risk from early development of atopic disease and reduce the severity of symptoms.     

Development of Asthma, Allergic Rhinitis and Atopic Dermatitis by the Age of Five Years: A Prospective Study of 543 Newborns

543 children were followed up from birth to 5 years of age. Children with a positive history of parents' atopy had a 51% occurrence of respiratory or dermal symptoms of atopy vs. a 19% occurrence among children with no family history of atopy. There was an association between asthma and allergic rhinitis while atopic dermatitis occurred equally in children with or without respiratory symptoms. The clinical course of atopic symptoms could not be correlated to the family history of atopy. The significance of date of birth, nasal eosinophilia and serum IgE levels seemed to be relatively low in atopic dermatitis while these parameters had a correlation to the development of respiratory atopies.     

Relation between airway responsiveness and serum IgE in children with asthma and in apparently normal children

BACKGROUND. Although asthma diagnosed by a physician is known to be related to serum IgE levels, it is not known whether there is a relation between the level of IgE and airway hyperresponsiveness to a methacholine challenge. The characteristics of asymptomatic persons that predispose them to airway hyperresponsiveness are also unknown. METHODS. We studied the relation between the serum total IgE level and airway hyperresponsiveness in the presence or absence of asthma and other atopic diseases in a birth cohort of children. Data from a questionnaire regarding respiratory symptoms, plus measurements of the serum total IgE level and airway responsiveness to inhaled methacholine, were obtained for 562 11-year-olds in New Zealand. RESULTS. The boys had a higher prevalence than the girls of current diagnosed asthma (13 percent vs. 6 percent), current symptoms of wheezing (22 percent vs. 15 percent), and airflow obstruction at base line (6 percent vs. 1 percent) and had a wider distribution of IgE levels, although mean IgE levels (120.8 IU per milliliter in the boys and 98.1 IU per milliliter in the girls) did not differ significantly between the sexes. The prevalence of diagnosed asthma was strongly related to the serum IgE level (P for trend less than 0.0001). No asthma was reported in children with IgE levels less than 32 IU per milliliter, whereas 36 percent of those with IgE levels greater than or equal to 1000 IU per milliliter were reported to have asthma. This relation with the serum IgE level was not explained by a concomitant diagnosis of allergic rhinitis or eczema. Airway hyperresponsiveness to a methacholine challenge also correlated very highly (P less than 0.0001) with the serum IgE level. This relation remained significant even after the exclusion of children with diagnosed asthma (P less than 0.0001) and of all children with a history of wheezing, allergic rhinitis, or eczema (P less than 0.0001). CONCLUSIONS. Even in children who have been asymptomatic throughout their lives and have no history of atopic disease, airway hyperresponsiveness appears to be closely linked to an allergic diathesis, as reflected by the serum total IgE level.     

Extraordinarily high serum IgE levels and consequences for atopic phenotypes.

BACKGROUND: IgE plays a central role in allergic diseases. Recent studies have postulated an association between serum IgE levels and bronchial asthma. OBJECTIVE: To examine the differences of atopic phenotypes in a group of individuals with extraordinarily high serum IgE levels (>10,000 kU/L) compared with children with moderately elevated IgE levels (400-1,000 kU/L). METHODS: We investigated 20 children with serum IgE levels greater than 10,000 kU/L and compared them with 56 age-matched children with serum IgE levels of 400 to 1,000 kU/L regarding prevalences of atopic dermatitis, bronchial asthma, allergic rhinoconjunctivitis, allergic sensitization, and history of anaphylaxis. RESULTS: The mean eczema severity score as determined by the Severity Scoring of Atopic Dermatitis Index was 56 vs 18 (P < 0.003), and anaphylactic reactions were reported in 20% of the group with very high serum IgE levels vs 7% in the group with moderate levels (P < 0.02). Sensitization to both aeroallergens and food allergens was detected in 80% of the group with very high serum IgE levels vs 32% of the group with moderate levels (P < 0.001). CONCLUSIONS: Our results indicate that children with very high serum IgE levels are at risk for anaphylactic reactions and more severe atopic dermatitis.     

Neonate blood IgE levels on filter paper as indicators of atopic disease

Measurements of IgE levels in the blood of neonates were investigated using filter paper for blood collection in mass screening of congenital metabolic disorders. Time-resolved fluoroimmunometric assay system for the measurement of filter paper blood IgE levels was also studied. In an analysis of the present results, IgE values of at least 0.015U/ml, the measurement limit, were considered as high. High IgE levels in filter paper blood were seen in 28 (7.2%) of the 389 cases. When the relation with serum IgE levels at 18 months of age was investigated in 134 of 389 subjects, high serum IgE levels were also found in about 86.7% of the subjects with high IgE levels in filter paper blood. In addition, when the relation between family history of atopic disease and presence of atopic disease in the first 18 months of age was investigated in 203 of the 389 subjects, about 90% of the subjects with a family history of atopic disease and high IgE levels in filter paper blood developed atopic disease. Since filter paper blood is routinely collected in Japan, IgE levels in this blood should be widely checked for the prediction of onset of atopic disease in infants.     

Fecal IgE levels in infants at 1 month of age as indicator of atopic disease

Fecal IgE levels were investigated in 165 asymptomatic infants at 1 month of age under two nutritional regimens, breast-feeding and formula feeding, and the possibility of predicting by fecal IgE levels the onset of atopic disease was studied in these infants. IgE levels were measured by time-resolved fluoroimmunometric assay. IgE antibodies are detectable in fecal extracts, and we have already reported that IgE levels are increased in food-allergy patients after administration of food allergens, and this increase in fecal IgE levels may be a specific consequence of the local immune response to food-allergen stimulation in the gut mucosa. The presence of atopic disease and the feeding method during the nursing period were surveyed by questionnaire in 89 of these 165 infants when they were 18 months old. In an analysis of the present results, IgE values above 0.015 U/ml, the lower limit of measurement, were considered to be high. Forty-eight (29%) of the 165 subjects showed a high fecal IgE level. Thirty-seven (35%) of 105 formula-fed infants had high fecal IgE levels, whereas only 11 (18%) of 60 breast-fed infants had high levels (P<0.05). With respect to atopic family history, 30(39%) of the 77 infants with atopic family history had high fecal IgE levels, as compared with 18 (20%) of the 88 infants without atopic family history (P<0.01). When the relationship between fecal IgE levels at 1 month of age and presence of atopic disease in the first 18 months was investigated, the prevalence of atopic disease was significantly higher in subjects with high fecal IgE levels (50%) than in subjects with low fecal IgE levels (14%) (P<0.01). We conclude that cow's milk proteins or dietary antigens in breast milk consumed by infants, in addition to genetic predisposition, may stimulate IgE immune response in the developmental gut mucosa, and that fecal IgE level at 1 month of age is an important and noninvasive factor for predicting the development of atopic disease during infancy and early childhood.     

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.     

Serum IgE in non-atopic adults and in dermatitis patients

Total serum IgE was determined with the PRIST technique, and specific reaginic antibodies against 10 allergens were measured in 163 healthy adults with no personal or family history of symptoms indicative of atopy (Group A). 103 non-atopic adults with a family history of atopic diseases were similarly investigated (Group B). When all subjects who at the second interview presented with a history of atopic symptoms and those with positive RAST results were excluded, the geometric mean serum IgE value for Group A was 14.5 (SD = 2) - 94.4 U/ml and for Group B 14.4 (SD = 2) - 130.2 U/ml. There was no significant difference in the IgE values between men and women. Subjects under 40 years of age had significantly higher IgE values than subjects over 40 years. In the series of 276 dermatitis patients the geometric mean IgE value for the men was significantly higher (46.8) than for the women (28.8 U/ml). There was a highly significant difference in the mean serum IgE levels between the patients with a personal history of atopic diseases and the other patients. Patients with present atopic disease had significantly higher mean IgE values than those with past atopic disease while no significant difference was discernible in the mean IgE levels between the non-atopic patients from atopic families and those with no personal and family atopy. Three years later, total serum IgE was controlled in subjects with initial IgE levels greater than 100 U/ml. During this time, eight subjects had developed an atopic disease. In most cases, there were only slight variations in the IgE values.     

Defining childhood atopic phenotypes to investigate the association of atopic sensitization with allergic disease

AIMS: Although atopic sensitization is common in childhood, its relationship to clinical allergic disease remains incompletely understood. We therefore sought to explore this relationship by defining sensitization based atopic phenotypes. METHODS: Children were recruited at birth (n = 1456) and reviewed at 1, 2, 4 and 10 years. Skin prick testing (SPT) to common allergens was done at 4 (n = 980) and 10 years (n = 1036) with lung function (n = 981), bronchial challenge (n = 784) and serum IgE (n = 953) testing at 10. Atopic phenotypes were defined, by sensitization pattern, for children with SPT at both 4 and 10 years (n = 823). RESULTS: Of phenotyped children, 68.0% were never atopic, 4.3% early childhood atopic (only atopic at age 4), 16.5% chronic childhood atopics (at 4 and 10 years) and 11.2% delayed childhood atopics (only at 10). Never atopics showed small but identifiable prevalence of allergic diseases such as asthma, eczema and rhinitis. Amongst allergen-sensitized subjects, aeroallergen predominated over food sensitization throughout childhood. Chronic childhood atopics showed highest prevalence of lifetime plus persistent wheeze, eczema and rhinitis, increased prevalence of aeroallergen sensitization, some evidence of persistent food sensitization, significantly greater cord IgE than never atopics (P = 0.006), plus higher total IgE (P < 0.001) and bronchial hyper-responsiveness (P < 0.001) at 10 years than other phenotypes. CONCLUSION: A proportion of childhood eczema, rhinitis and asthma is nonatopic. The commonest childhood pattern of atopy is chronic sensitization, associated with early, persisting and clinically significant allergic disease. The currently accepted childhood 'Allergic March' may oversimplify the natural history of childhood atopy and allergic disease.     

Elevated cord serum IgE increases the risk of aeroallergen sensitization without increasing respiratory allergic symptoms in early childhood

BACKGROUND: Increasing prevalence of allergic disorders has focused attention on primary prevention. There is a need to improve the accuracy of early-life predictors of atopy so that the at-risk population can be accurately defined and preventive measures instituted. OBJECTIVE: The predictive capacity of elevated cord IgE, with or without family history of atopy, to allergic symptoms and skin prick test (SPT) sensitization is evaluated in a birth cohort followed up prospectively for 4 years. METHODS: A birth cohort of 1456 consecutively born children was recruited in 1989. Data were collected on family history of atopy and cord serum total IgE (cord IgE) was measured. Of these, 1218 children were seen in the clinic at 4 years to determine the development of symptoms and signs of allergic disease and 981 were skin tested to a range of common food and aeroallergens. RESULTS: Of 1218 children reviewed at age 4 years, 218 (17.8%) had symptoms of respiratory allergy and, of those skin tested (n = 981), 192 (19.6%) reacted positively. Twice as many children with elevated cord IgE (>/= 0.5 kU/L) at birth became sensitized to aeroallergens by age 4 years (34.8% vs 17.3%, P < 0. 001). Positive predictive value (PPV) of elevated cord IgE for the development of aeroallergen sensitization was better than that of family history of atopy (34.8 vs 22.6%). Combining paternal atopy with elevated cord IgE substantially increased the predictive capacity (PPV 77.8%). Cord IgE levels did not correlate with clinical asthma or rhinitis at age 4 years and PPV for allergic respiratory symptoms remained poor at all cutoffs. CONCLUSION: Cord IgE is better than family history for predicting atopy as defined by allergen sensitization and this predictive value can be further increased by combining cord IgE with paternal atopy.     

A survey of nonatopic and atopic children and adults for the presence of anti-IgE autoantibodies

The prevalence of naturally occurring anti-IgE autoantibodies was assessed by surveying 387 sera from atopic, nonatopic, and autoimmune patients. A significant number of children (28.5%) and adults (20%) with no history of allergy had high levels of autoanti-IgE. The level of autoantibodies to IgE in children with clinical asthma or atopic eczema was not significantly elevated over normal. Similarly, adults with atopic asthma, allergic rhinitis, or urticaria or sera from individuals with rheumatoid arthritis or systemic lupus erythromatosis showed no significant elevation of auto-anti-IgE. In contrast, 82% of adults with eczema had medium to high levels of auto-anti-IgE and the mean concentration in sera was significantly (P less than 0.01) raised. The relevance of auto-anti-IgE in atopic eczema is discussed.     

Relationship between active and passive smoking and total serum IgE levels in Japanese women: baseline data from the Osaka Maternal and Child Health Study

BACKGROUND: Many studies have shown that cigarette smoking is associated with elevated concentrations of total serum IgE. Few studies, however, have examined total IgE in relation to passive smoking exposure, especially in adults. This cross-sectional study investigated the association of active and passive smoking exposure with levels of total serum IgE in Japan. METHODS: Study subjects were 981 pregnant women in Osaka. Total IgE levels were measured using UniCAP 1000 and were defined as elevated if they exceeded 170 ml/UI. Age, gestation, parity, family history of asthma, atopic eczema and allergic rhinitis, indoor domestic pets, family income, education and the mite allergen level in house dust were selected as potential confounding factors. RESULTS: Current smoking of at least 15 cigarettes a day and 8.0 or more pack-years of smoking were independently related to an increased prevalence of elevated total serum IgE (adjusted odds ratios 3.40 and 2.51, 95% confidence intervals 2.12-5.47 and 1.55-4.06, respectively), and both cigarette smoking status and pack-years of smoking were significantly positively associated with total serum IgE levels, especially in subjects with a positive familial allergic history. There was no measurable association of exposure to environmental tobacco smoke (ETS) at home or at work with total serum IgE concentrations among those who had never smoked. CONCLUSIONS: Our results corroborate a positive relationship between active smoking and total serum IgE levels; however, this study failed to substantiate a positive association of ETS exposure with total IgE. Investigations with more precise and detailed exposure measurements are warranted.     

Breastfeeding and the prevalence of symptoms of allergic disorders in Japanese adolescents

BACKGROUND: Environmental factors acting early in life are key determinants of the incidence of allergic disease. Whether breastfeeding is protective against allergic disorders remains controversial. OBJECTIVE: The present cross-sectional study examined the relationship between feeding patterns in the first 3 months of life and the prevalence of symptoms of wheeze, atopic eczema, and rhinoconjunctivitis during the past 12 months in Japanese adolescents. METHODS: The subjects were 5614 of 9008 students (62%) aged 12-15 years from all public junior high schools in Suita, Japan in 2001. This study used the diagnostic criteria of the International Study of Asthma and Allergies in Childhood. Adjustment was made for gender, grade, number of older siblings, and parental history of allergy. RESULTS: Feeding pattern was unrelated to the prevalence of wheeze or rhinoconjunctivitis. The prevalence of atopic eczema was significantly higher in children who had been breastfed than in artificial milk feeders (adjusted odds ratios = 1.40 and 1.56, 95% confidence intervals: 1.01-1.98 and 1.13-2.22 for mixed milk intake and breastfeeding only vs. artificial milk consumption, respectively; P = 0.01 for linear trend). When children were divided according to a positive or negative allergic history in at least one parent, an increased prevalence of atopic eczema associated with breastfeeding was found in children with a negative parental allergic history compared with those with a positive parental allergic history. CONCLUSION: The findings suggest that breastfeeding may be associated with an increased prevalence of atopic eczema, especially among children without a parental history of allergy.     

Clinical features of atopic dermatitis and a family history of atopy

In 365 children and 213 adults the characteristics of atopic dermatitis isolated by Hanifin and Rajka were analysed in relation to a family history of allergy. A positive history in both parents and/or their families was associated with higher IgE titres, earlier appearance of skin changes, more frequent occurrence of urticaria, allergic respiratory diseases, cheilitis, and, in women, nipple eczema. These changes were less frequent and the IgE titre was lower in patients with one atopic parent, and even less frequent (or lower IgE titre) in patients with no family history of atopic disease, although the latter difference was sometimes slight.     

Parental history of atopic disease and concentration of cord blood IgE

Background A family history of atopy, and cord blood immunoglobulin E concentration, have been shown to be predictors of atopic disease in children. Several studies have suggested that parental atopy may be related to newborn immunoglobulin E. Objective The purpose of our analysis was to evaluate whether parental history of allergic disease was associated with cord blood immunoglobulin E concentration. Methods The study subjects were from a defined population of 777 newborns delivered between 1987 and 1989. The mothers of these children completed a questionnaire during pregnancy concerning themselves and the child's father, including parental history of physician diagnosis of allergic diseases (allergies, hay fever and asthma). Total immunoglobulin E levels were quantitated in cord blood samples with an enzyme-hnked immunoassay. Results Median cord blood immunoglobulin E concentration was higher among infants whose mothers had a history of atopic disease, particularly for those with a history of asthma (P<0.022) and allergen immunotherapy (P<0.016) vs infants whose mothers had no history of any atopic disease. Comparing all babies with a maternal history of asthma, to babies where neither parent had a history of any atopic disease, the median cord blood immunoglobulin E was significantly higher (0.36IU/mL vs 0.21 IU/mL; P<0.009). This association was found only among female infants (0.49IU/mL vs 0.20 IU/mL; P<0.001). Conclusion Maternal, but not paternal, history of atopic disease was associated with an elevated immunoglobulin E among newborns. For maternal asthma, this association was only evident in infant girls.     

29例特应性皮炎患者血清总IgE水平的检测

文本用双抗体夹心酶联免疫吸附试验(ELISA)测定了21例无过敏史和寄生虫卵检查阴性的健康对照及29例临床确诊为特应性皮炎(AD)患者的血清总IgE水平。结果表明:(1)AD病人血清总IgE水平明显高于正常对照,经统计学处理差别非常显著(P<0.01);(2)IgE水平与临床症状有呈正相关的倾向,症状严重者IgE水平较高,反之较低,但其差别未达到统计学上有意义的程度;(3)IgE水平与家族过敏史的相关性不明显,具有家族过敏史的AD病人其血清总IgE水平较无家族史者高,但无统计学意义;IgE水平与个人过敏史的关系亦不明显;(4)並非所有AD患者的血清总IgE水平都高于对照组的几何均值,对其可能的原因进行了分析。     

Predictors of atopy in HIV-infected patients.

BACKGROUND: Some studies have reported an increase of atopy in HIV-infected (HIV+) patients, but the cause still remains unclear. OBJECTIVE: To determine the prevalence of atopy in HIV+ patients and to investigate its predictors. METHODS: Seventy-four HIV+ hospitalized patients (46 of them with AIDS) were studied prospectively for the presence of atopy, based on immediate hypersensitivity to common allergens by prick test. Serum immunoglobulins, specific IgE, lymphocyte subsets, and the expression of low affinity IgE receptor (CD23) on B cells were determined. RESULTS: Thirty-one percent of patients presented IgE values greater than 150 ku/L (39% of patients without AIDS and 26% of AIDS patients; P = .23) and 47% showed an increase (> or = 2%) in the percentage of CD23+ B cells. Non-AIDS patients had higher IgE values than AIDS patients (346 +/- 605 versus 175 +/- 276; P = .16). Atopy prevalence was higher in non-AIDS than in AIDS patients (28% versus 11%; P = .06). Specific IgE agreed with positive prick test in 58% of cases. Multivariate analysis showed that a personal history suggestive of allergic disease and IgE > 150 ku/L were predictors of atopy, while gender, risk group, CD4+ T cells, CD23 expression on B cells, and AIDS were not associated. CONCLUSIONS: HIV+ patients present a higher prevalence of atopy in early stages of HIV infection than general population. Since allergic reactions could accelerate HIV-infection by increasing type 2 cytokines, it is important to evaluate the atopic state in HIV+ patients with IgE > 150 ku/L or with suggestive allergic history in order to prevent it.     

Aging and serum immunoglobulin E levels, immediate skin tests, RAST

The changes of the serum IgE levels, specific immediate skin-test responses, and RAST measurements with age were evaluated. A total of 331 unrelated individuals were studied, consisting of 166 subjects with ragweed allergic rhinitis and/or asthma, 67 with idiopathic (intrinsic) asthma, and 98 who appeared in good health with no clinical evidence of atopic diseases. All subjects were evaluated by history and physical examination, intradermal skin testing to the common aeroallergens, measurements of IgE antibody to common aeroallergens with the RAST, and serum IgE levels. Results demonstrated a significant decrease in serum IgE levels with aging in atopic individuals. This decline was exponential in character. In addition, a tendency for RAST and immediate type skin-test responses for selected antigens and histamine to decrease with age was observed.     

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.