tIgE Levels Research Articles

Pitfalls and peculiarities in chlorhexidine allergy

Chlorhexidine (CHX) is a synthetic biguanide available in different forms (diacetate, dihydrochloride, and digluconate) and used as an antiseptic. In the past few years, there has been a substantial increase in the number of CHX-containing products used in health care. Hypersensitivity reactions to CHX are increasingly reported and include allergic contact dermatitis, photosensitivity, fixed drug eruptions, asthma, and lifethreatening anaphylaxis. Here, we report 3 cases of anaphylaxis due to CHX with a particular course, highlighting possible pitfalls and peculiarities in CHX allergy.

Influence of Omalizumab on Allergen-Specific IgE in Patients with Adult Asthma

Background: Omalizumab, an anti-immunoglobulin E (IgE) monoclonal antibody, inhibits the binding of circulating IgE to mast cells and basophils, resulting in fewer episodes of airway inflammation, asthma symptoms and exacerbations in patients with severe allergic asthma. Treatment of patients with asthma using omalizumab increases serum total IgE (tIgE) levels. However, little is known about the influence of omalizumab on allergen-specific IgE (sIgE). Methods: tIgE and sIgE in 47 adult patients with severe asthma were measured with a fluorescent enzyme immunoassay (ImmunoCAP-FEIA) before and after omalizumab treatment. Results: Treatment with omalizumab increased tIgE and sIgE levels. The increases in sIgE by class category after omalizumab treatment were positively correlated with baseline sIgE positivity before treatment. The mean changes in sIgE levels after omalizumab treatment were also correlated with baseline sIgE levels before treatment. The mean changes in tIgE levels were positively correlated with the mean changes in IgE levels against Dermatophagoides pteronyssinus, crude house dust, Japanese cedar and moth. Omalizumab markedly influenced the negative-to-positive seroconversion rate for IgE against Japanese cedar (30.8%), Candida (29.0%) and moth (28.0%). Finally, all patients with negative-to-positive seroconversion for Japanese cedar-specific IgE had cedar pollinosis before beginning omalizumab treatment. Conclusions: The changes in sIgE levels after omalizumab treatment may be dependent on the baseline sIgE levels. Our data may indicate the presence of undetectable but functional sIgE.

Selected immunological parameters in clinical evaluation of patients with atopic dermatitis.

IntroductionIt has been suggested that soluble immune receptors (SIRs) such as sCD25 and sCD30 may serve as potential biomarkers in evaluation of atopic dermatitis (AD). Previous studies clearly indicated that serum levels of interleukin (IL)-13 and total IgE (tIgE) might be potentially useful in the evaluation of patents with AD.AimTo evaluate whether serum levels of sCD25 and sCD30 are suitable biomarkers of AD. Moreover, we have decided to estimate the usefulness of tIgE and IL-13 serum level determination in the evaluated population.Material and methodsA group of 102 AD patients was investigated. Serum concentrations of sCD30, sCD25, IL-13 and tIgE were measured. The clinical phenotype of AD was classified as extrinsic (ADe) or intrinsic (ADi) based on the presence of IgE. Statistical analysis was performed to estimate correlations between obtained results and clinical features of the population such as AD phenotype, age, disease extent and severity.ResultsExtrinsic AD was diagnosed in 71% of patients, while ADi phenotype was observed in 29% of the investigated population. A negative correlation between serum levels of sCD25 and sCD30 and disease severity as well patients’ age was established. Serum levels of IL-13 did not reach the cut-off point set by the manufacturer. A positive correlation between serum levels of total IgE and disease severity and patients’ age was observed.ConclusionsThis paper shows that serum levels of sCD25 and sCD30 as well as tIgE are age dependent. Determination of serum levels of sCD25, sCD30 and IL-13 is not useful in everyday practice.

Asthma severity, not asthma control, is worse in atopic compared with nonatopic adolescents with asthma

BackgroundThe effects of atopic and nonatopic asthma phenotypes on asthma morbidity are unclear. Moreover, asthma morbidity in patients without atopy might be mediated by immunoglobulin E (IgE). ObjectiveTo determine differences in morbidity in patients with asthma with and without atopy in a population of inner-city adolescents with asthma and to assess the impact of total IgE (tIgE) in this population. MethodsData were obtained from 546 inner-city adolescents in the Asthma Control Evaluation study. A positive skin prick test reaction to 14 aeroallergens and specific IgE to 5 aeroallergens determined atopic status. High (≥75th percentile) and low (≤25th percentile) tIgE levels were categorized. Asthma control (Asthma Control Test) and asthma severity (Composite Asthma Severity Index [CASI]) were measured at multiple time points over 1 year. Fractional exhaled nitric oxide (FeNO) and measurements of morbidity also were collected. Multivariable and repeated measures analyses modeled the relation between atopic status and morbidity. ResultsBaseline CASI scores increased 0.90 point (P < .05) and FeNO increased 0.85 natural logarithmic unit (P < .001) in participants with vs without atopy. Repeated measures analyses showed consistent results. Participants without atopy and increased tIgE had FeNO 0.73 natural log unit higher (P < .01) than low tIgE and a nonsignificant increase in CASI. The CASI score and FeNO levels were higher for high than for low tIgE in participants with atopy. ConclusionIn this population, participants with atopic asthma had worse asthma severity and higher FeNO compared with those with nonatopic asthma, but no difference in control. In all participants, higher tIgE indicated worse severity and higher FeNO. In this population, asthma severity and FeNO might be mediated by IgE in the 2 asthma phenotypes.

Total Immunoglobin E: Clinical Utility and Measurement

Total Immunoglobulin E (tIgE) is still being ordered alone or along with allergen specific IgE as first line test to diagnose allergic diseases in primary care settings. It has been well established that elevated serum tIgE levels are of very limited clinical utility in allergy as it does not give any information of sensitizing allergens in an individual. TIgE levels are shown to be useful to screen for presumptive diagnosis of IgE myeloma (myeloma that selectively produce IgE par protein). Though tIgE immunoassay are one of the most well standardized assays with high precision and reproducibility, its main utility appears to be limited to evaluate and monitor patients as candidates for the receiving anti-IgE therapy. TIgE is a nonspecific allergy marker and is replaced by more specific and sensitive markers as specific-IgE (sIgE) and component-resolved diagnostics.

Association of serum 25-hydroxyvitamin D with serum IgE levels in Korean adults.

Studies about the association between vitamin D and allergic disease and the immune-modulatory function of vitamin D have increased in the recent years. However, not enough studies have been conducted for concrete conclusion about the association vitamin D and allergy. We investigate the association between serum immunoglobulin E (IgE) and serum 25-hydroxyvitamin D (25(OH)D) levels in Korean adults. We used data of 1969 subjects from the 2010 Korean National Health and Nutrition Examination Survey. Total IgE, Dermatophagoides farinae (Df)-specific IgE, and serum 25(OH)D levels were analyzed. Other variables included sex, age, body mass index, smoking history, and economic status. Adjusted regression analysis was used to examine the independent association of 25(OH)D with serum IgE levels. When we divided all subjects into four groups according to the serum 25(OH)D level: Q1 (lowest), Q2, Q3, and Q4 (highest), the median TIgE level increased with higher quartiles in the Kruskal-Wallis test (p<0.001). Also, the prevalence of Df sensitization was highest in Q4. Serum vitamin D was positively associated with logarithmic transformed total IgE with base of 10 (LogTIgE) (coefficient (B), 0.011; 95% confidence interval, 0.001-0.021). Furthermore, a positive association between 25(OH)D and LogTIgE was found only in men with Df sensitization, but not in men without Df sensitization and women with/without Df sensitization. However, the mean serum 25(OH)D level was significantly lower in participants who were clinically diagnosed with asthma or atopic dermatitis than participants without a history of asthma or atopic dermatitis, respectively. Serum 25(OH)D levels were positively associated with total IgE levels. Furthermore, the association between serum 25(OH)D and total IgE levels could vary depending on sex or allergic sensitization. But, the mean serum 25(OH)D level was lower in participants with asthma or atopic dermatitis history than participants without history of asthma or atopic dermatitis. Prospective further studies will be required to verify this discrepancy.

Total serum IgE level in COPD patients

ObjectiveThe Dutch Hypothesis has been used to suggest that Asthma and COPD may be considered as different expressions of one disease entity. The purpose of this study is to evaluate the levels of IgE in COPD patients and its relation with respiratory symptoms and lung functions this may be a suggestive of atopy as a mechanism for initiation of their exacerbations. MethodsA cross-sectional case-control study was conducted on 50 subjects recruited from the outpatient clinic (11 healthy volunteers, 39 diagnosed as COPD) COPD patients (31 males (79%) and 8 females (21%)) diagnosed as mild, moderate and severe. The studied groups were also divided according to total serum IgE levels and compared in demographic data, clinical data, spirometric data, and HRCT findings. ResultsCOPD patients with elevated IgE had a longer history of illness, high smoking index, higher number of exacerbation in the last year, and more lower FEV1.HRCT finding in both groups was hyperinflation was high in COPD patients with normal IgE levels, 10 cases (45%), while bronchiectasis was higher in COPD patients with elevated IgE, 7 cases (41%). Sputum culture was positive for aspergillosis in 5 cases (29%) in COPD patients with elevated IgE. ConclusionsThere was a high prevalence of elevated serum T-IgE in patients with COPD but without obvious atopy. Serum T-IgE levels were found to be associated with symptoms such as dyspnea and impairment of lung function. Recurrent exacerbation of COPD is believed to accelerate disease progression and impairment of pulmonary function.

Correlations between basophil activation, allergen-specific IgE with outcome and severity of oral food challenges

BackgroundDouble-blinded, placebo-controlled food challenges (DBPCFCs) remain the gold standard for diagnosing food allergies. Skin prick tests (SPTs) and allergen-specific IgE (sIgE) are routinely used in medical practice but are not sufficient to predict severity of clinical reactivity. ObjectiveTo compare the utility of SPT wheal diameter, sIgE, allergen-specific IgG4 (sIgG4), total IgE (tIgE), sIgE/sIgG4 and sIgE/tIgE ratios, peanut component-specific IgE, and basophil activation in predicting outcome and severity of reactions at DBPCFCs. MethodsSixty-seven subjects (12–45 years old) underwent DBPCFCs for peanut, tree nut, fish, shrimp, and/or sesame as part of screening for enrollment in a clinical trial. The SPT, sIgE, tIgE, sIgG4, and peanut component-specific IgE (if applicable) levels were measured. CD63 upregulation on basophils in response to in vitro allergen challenge was analyzed by flow cytometry. Correlations between these measurements and DBPCFC severity scores were analyzed. ResultsThe SPT and sIgE showed a weak correlation with DBPCFC severity scores, but tIgE and sIgG4 did not. The sIgE/sIgG4 ratio differentiated between positive and negative reactions but did not correlate with DBPCFC severity scores. A low positive correlation was seen between DBPCFC severity score and Ara h 2 IgE, whereas a low negative correlation with Ara h 8 IgE was observed. Basophil activation was positively correlated with DBPCFC severity scores. Receiver operating characteristic curves showed basophil reactivity had the largest area under the curve at 0.904 and sIgE at 0.870. ConclusionThese results indicate that basophil activation testing can enhance discrimination between allergic and nonallergic individuals and could serve as an additional tool to predict clinical severity.

Longitudinal observation of children with enhanced total serum IgE

BackgroundLong-term studies on the evolution of elevated total IgE (tIgE) concentration are in demand. ObjectiveTo investigate the prevalence of allergic diseases and influential factors in children with high tIgE levels during a 5-year period. MethodsChildren with high tIgE levels (>100 IU/mL) were study subjects. After the 5-year follow-up, an interview with the parents, clinical examination, and evaluation of tIgE and specific IgE (sIgE) to selected food and inhalant allergens were performed. ResultsThe mean tIgE decreased significantly after 5 years in girls and boys regardless of the place of residence. Monosymptomatic patients accounted for most cases throughout the study, with the highest tIgE level at the beginning. After follow-up, the percentage of polysymptomatic patients increased. Their mean tIgE level was significantly higher than in the other groups. After follow-up, 11.7% of participants remained asymptomatic, and another 11.7% reported relief from symptoms. Allergy symptoms persisted in most children with normal tIgE levels. The 2-allergen sensitization was the most common through the study. Only patients sensitized to 4 allergens had unchanged levels of mean tIgE after follow-up and those with the highest mean tIgE level had a newly diagnosed sensitization to at least 1 allergen. A significant decrease of sIgE level was observed for food allergens. The values of sIgE to inhalant allergens even increased after the 5-year follow-up, despite decreased tIgE levels. ConclusionIn children with allergy and an elevated concentration of tIgE, the increasing or stable value of tIgE could be a useful parameter for the prediction of the development of polysymptomatic allergy.

Campylobacter jejuni infection and IgE sensitization in up to 2-year-old infants.

The "hygiene hypothesis" addresses the correlation between the occurrence of atopy and the frequency of infections in the earliest age, explaining an increase in the incidence of atopic diseases by living in good, infection-free, hygienic conditions. The aim of our study was to determine the conection between atopy and Camplobacter infection, and to analyze the association between serum concentrations of total IgE and Campyobacter infection in relation to atopy in children up to two years. A case control study was conducted with the sample of 98 infants of the average age of 8 months. Total serum IgE and Phadiatop infant multi-test were determined on Immunocap-100 (Phadia AB, Uppsala, Sweden). The presence of atopy was determined by detection of serum-specific IgE > 0.35 kUA/L (Phadiatop infant positive) and serum IgM, IgA, IgG levels against C j uni were determined by a quantitative immuno-enzyme test--SERION ELISA classic. Total IgE cut-off values > 15 kU/L point to atopy in infants, and tIgE cut-off values > or = 8.1 kU/L pointed to a Cj/uni infection in infants. Within the group of atopic children, tIgE levels > 29.8 kU/L point to C. jejuni infection, and within the group of non-atopic children, tIgE levels > or = 5.9 kU/L point to infection. Enteritis is not a predictor of C jejuni infection, because of a high frequency of asymptomatic cases of infection. The risk factors for C. jejuni infection are age and tIgE, and the protective factors are breastfeeding and atopy. C. jejuni infection increases the total serum IgE level, which is pre- dictive of infection, regardless of the presence of atopy. The presence of symptomatic C. jejuni infection reduces the risk of atopy in a child of the age of 5-24 months by the factor of 10.

Predictive Factors for Clinical Response to Allergy Immunotherapy in Children with Asthma and Rhinitis

Background: To date, no predictive methods for the clinical response to allergy immunotherapy (AIT) are available. We sought to evaluate the pretreatment parameters used in diagnosing allergic asthma and/or rhinitis including allergen skin-prick test responses, serum specific and total IgE (sIgE and tIgE) levels and blood eosinophil counts, and to identify whether these can be used to predict clinical effectiveness in children treated with immunotherapy. Methods: This study involved 185 children who had undergone 3 years of standardized-quality house-dust mite subcutaneous immunotherapy. Clinical characteristics and laboratory parameters were analyzed. A multivariate unconditional logistic regression model and receiver operating characteristic curves were used. Predicted probabilities and predictive areas under the curve were calculated. Results: The clinical response to AIT was effective in 129/185 (69.7%) patients. Four variables were associated with clinical response by multivariate logistic analysis: tobacco smoke exposure [odds ratio (OR) 2.845 and 95% confidence interval (CI) 1.147-7.058; p = 0.024], a family history of atopy (OR 2.881 and 95% CI 1.240-6.692; p = 0.014), a serum tIgE level ≥965 kU/l (OR 5.917 and 95% CI 2.320-15.089; p = 0.000) and an sIgE/tIgE ratio ≥6% (OR 0.336 and 95% CI 0.124-0.911; p = 0.032). The sensitivity and specificity of the area under the curve of the serum tIgE were higher than those of serum sIgE and sIgE/tIgE ratio alone. Conclusion: Tobacco smoke exposure, atopic family history, serum tIgE and sIgE/tIgE ratio were in significant correlation with clinical response to AIT in children, which may be helpful for patient selection before immunotherapy. The serum tIgE is superior to both the serum sIgE/tIgE ratio and sIgE levels alone in predicting clinical effectiveness.

Aspergillus Sensitization or Carriage in Cystic Fibrosis Patients

Aspergillus fumigatus (Af) sensitization and persistent carriage are deleterious to lung function, but no consensus has been reached defining these medical entities. This work aimed to identify possible predictive factors for patients who become sensitized to Af, compared with a control group of non-sensitized Af carriers. Between 1995 and 2007, 117 pediatric patients were evaluated. Demographic data, CFTR gene mutations, body mass index and FEV1 were recorded. The presence of Af in sputum, the levels of Af-precipitin, total IgE (t-IgE) and specific IgE to Af (Af-IgE) were determined. Patients were divided into 2 groups: (1) "sensitization": level of Af-IgE > 0.35 IU/mL with t-IgE level < 500 IU/mL and (2) "persistent or transient carriage": Af-IgE level ≤ 0.35 IU/mL with either an Af transient or persistent positive culture. A survival analysis was performed with the appearance of Af-IgE in serum as an outcome variable. Severe mutation (hazard ratio = 3.2), FEV1 baseline over 70% of theoretical value (hazard ratio = 4.9), absence of Pa colonization, catalase activity and previous azithromycin administration (hazard ratio = 9.8, 4.1 and 1.9, respectively) were predictive factors for sensitization. We propose a timeline of the biological events and a tree diagram for risk calculation. Two profiles of cystic fibrosis patients can be envisaged: (1) patients with nonsevere mutation but low FEV1 baselines are becoming colonized with Af or (2) patients with high FEV1 baselines who present with severe mutation are more susceptible to the Af sensitization and then to the presentation of an allergic bronchopulmonary aspergillosis event.

Allergic airway diseases in a tropical urban environment are driven by dominant mono‐specific sensitization against house dust mites

BackgroundSoutheast Asian populations are increasingly affected by allergic airway diseases. Etiology and specific causes, however, are still unknown. The aim of this study is therefore to identify allergens and risk factors for the high prevalence of allergic airway disease in the tropical urban environment.MethodsSymptoms of allergic rhinitis (AR), asthma, and allergic dermatitis were recorded in two independent cohorts of 576 and 7373 ethnic Chinese individuals living in Singapore. Reactivity against common allergens was determined by skin prick tests (SPT); specific immunoglobulin E (sIgE) titers against 12 common allergens, as well as total serum IgE (tIgE), were measured in the smaller cohort.ResultsImmunoglobulin E sensitization was almost exclusively directed against house dust mite (HDM) allergens. More than 80% of individuals were HDM-sIgE positive. Of these, less than 30% also had sIgE for other allergens, and similarly, few of the HDM-sIgE-negative individuals reacted to other allergens. Titers for HDM-sIgE were 8–30 times higher than other non-HDM allergen titers and correlated directly with total serum tIgE levels. Migrants from nontropical countries typically arrived with low or undetectable HDM-sIgE but developed substantial titers in a time-dependent fashion. Importantly, prolonged stay in Singapore also resulted in the manifestation of AR and asthma symptoms, contributing to some of the highest national prevalence rates worldwide.ConclusionIn a tropical urban environment, the allergic response is dominated by a single allergen class. The mono-specific IgE sensitization against HDM translates into increased prevalence of allergic airway diseases, which now impact a large proportion of the population in Singapore.

Analysis of comorbidities and objective parameters in refractory chronic rhinosinusitis

The objective of this study was to construct the clinical profile of patients with chronic rhinosinusitis (CRS) with/without polyposis undergoing revision sinus surgery and to evaluate the relationship of polyposis, asthma, acetylsalicylic acid (aspirin) (ASA) sensitivity, inhalant allergies, and previous sinus surgery on disease severity as measured by objective parameters. Cross-sectional study. Two-hundred twenty-five patients were accrued at a tertiary care academic center. Categorical factors recorded included presence of polyps, asthma, inhalant allergy, and ASA sensitivity. Continuous variables assessed included mean number of previous sinus surgeries, Lund-Kennedy endoscopy score, Lund-Mackay computed tomography (CT) score, absolute eosinophil count (AEC), and total immunoglobulin E (tIgE) level. Statistical analysis was performed to analyze the impact of polyposis, asthma, inhalant allergy, and ASA sensitivity on objective parameters. The mean number of previous surgeries was also correlated with objective parameters. The mean age was 50.1 years with a male:female ratio of 1.1:1. The overall prevalence of polyposis, asthma, inhalant allergy, and ASA sensitivity was 56.4%, 48.4%, 38.7%, and 16.0%, respectively. The mean endoscopy and CT scores were 9.0 (± 4.0) and 11.4 (± 5.8), respectively. The mean AEC and tIgE were 0.4 k/μL (± 0.4) and 161.4 IU/mL (± 251.4). The mean number of previous endoscopic sinus surgeries was 1.8. Patients with CRS with polyposis had a statistically significant increase in presence of asthma (odds ratio [OR]: 7.5, P < .0001), inhalant allergy (OR: 3.6, P < .0001), and ASA sensitivity (OR: 78.6, P < .0001). Patients with polyposis had a statistically significant increase in endoscopy score (P < .0001), CT score (P < .0001), AEC (P < .0001), and tIgE (P = .0002). Patients with asthma had a statistically significant increase in endoscopy (P < .0001) and CT scores (P < .0001), AEC (P < .0001), and tIgE (P = .0002). Patients with inhalant allergy had a statistically significant increase in endoscopy (P = .0069), CT scores (P = .0017), and tIgE (P = .0084) but not AEC (P = .1492). Patients with ASA sensitivity had a statistically significant increase in endoscopy score (P < .0001), CT score (P < .0001), and AEC (P = .003) but not tIgE level (P = .186). The number of previous surgeries had a statistically significant correlation with endoscopy (P = .006) and CT scores (P = .03) but not AEC (P = .48) or tIgE (P = .66). The current analysis constructed the clinical profile of the recalcitrant CRS patient undergoing revision sinus surgery. In general, this patient group has a high prevalence of polyposis, asthma, inhalant allergy, ASA sensitivity, and elevated disease burden as measured by objective measures. The polyp phenotype signifies statistically higher prevalence of associated comorbidities and greater objective disease severity. The presence of asthma, inhalant allergy, and ASA sensitivity also predicts statistically higher disease burden. The endoscopy and CT scores statistically correlate with the number of previous surgeries. 4 Laryngoscope, 123:E1-E11, 2013.

Impact of allergic rhinitis and specific subcutaneous immunotherapy on peripheral blood basophils of patients sensitized to Dermatophagoides pteronyssinus

BackgroundBasophils are important effectors cells in allergic rhinitis (AR) since they are involved in immunoglobulin (Ig) E – mediated inflammation and in the release of pro-inflammatory mediators. Specific subcutaneous immunotherapy (SCIT) provides clear immunologic modulation in some immune cells, however its systemic effects on basophils are not well known.MethodsPeripheral blood (PB) samples from 43 patients with allergic rhinitis mono-sensitized to Dermatophagoides pteronyssinus (Dpt) [33 of them under SCIT with allergoid Dpt extract, in maintenance dose (SCIT), with evaluation just before SCIT injection (SCIT-T0) and 4 hours later (SCIT-T4) and the other 10 Dpt allergic patients never having, in the past, undergone specific immunotherapy treatment (NSIT)], and 15 healthy age- and gender-matched controls (HG), were analyzed. For each sample, the total (t-IgE) and specific IgE (s-IgE) was performed, as well as, the relative frequency and absolute number of PB basophils and receptor-bound IgE and IgG expression were evaluated by flow cytometry and the Histamine N-methyltransferase (HNMT) and tryptase α/β1 (TPSAB1) gene expression was assessed by real-time PCR.ResultsHigher levels of receptor-bound IgE were observed in SCIT patients, which are correlated with the levels of serum t-IgE and s-IgE, whereas no significant differences were observed for receptor-bound IgG. Regarding HNMT mRNA expression, significantly lower expression levels were detected in AR patients compared to HG, independently of type of therapy. Moreover a negative correlation was found between HNMT gene expression and time under SCIT. Conversely, tryptase gene expression was significantly up-regulated in NSIT when compared to HG; however in SCIT patients, tryptase gene expression was significantly decreased than in NSIT patients. No differences were found for any parameter between SCIT-T0 and SCIT-T4 with exception of a transient increased expression of tryptase in SCIT-T4.ConclusionPB basophils from patients with AR show altered functional features, which seems to be influenced by SCIT, suggesting that these cells could be useful to clarify the SCIT triggered mechanisms at a systemic level.

Activation of Eosinophils Is More Closely Linked with Interleukin-5 and Nitric Oxide Production than Tumor Necrosis Factor-α and Immunoglobulin E Levels

Patients were eligible if they had the following: (1) a documented clinical history of acute asthma, (2) positive results for sIgE test (aeroand/or food allergens according to the ImmunoCAP test), and (3) elevated serum total IgE (tIgE) levels to confirm allergy. The exclusion criteria were as follows: (1) medication history including corticosteroids or histamine antagonists, (2) concurrent systemic infection with fever (>37.5 ° C), or (3) chronic illness. The following parameters were measured: eosinophil parameters (ECP and ECP/Eo ratio), IgE-related parameters (sIgE score and tIgE level), cytokines (IL-5 and TNF-α), and inflammatory parameters [NOx metabolites and high-sensitivity C-reactive protein (hsCRP)]. The serum ECP concentration was measured using a solid-phase, 2-site chemiluminescent immunometric assay on an Immulite 2000 analyzer (Siemens Healthcare Diagnostics, Tarrytown, N.Y., USA). The cutoff limit for a positive serum ECP result was set at >19 μg/l on the basis of the manufacturer’s instruction. sIgE was measured for 2 major inhalant allergens (Dermatophagoides pteronyssinus and D. farinae) and 2 food allergens (egg white and cow’s milk) using a fluoroenzyme immunoassay system (ImmunoCAP 100, Phadia AB, Uppsala, Sweden). sIgE concentrations >0.35 kU/l Eosinophils contain several proinflammatory mediators and are implicated in the initiation of diverse inflammatory responses [1] . Eosinophil cationic protein (ECP) is produced in eosinophilic progenitors, stored in cytoplasmic granules of mature eosinophils, and released from activated eosinophils [2, 3] . The ratio of serum ECP concentrations to peripheral blood eosinophil counts (ECP/Eo ratio) reflects the number of ECP molecules per circulating eosinophil, which is regarded as a potential indicator of eosinophil activation [4, 5] . Few studies have closely examined the relationships between the activation of eosinophils and the production of nitric oxide (NOx) and cytokines. The present study investigated the associations between eosinophil activation and the levels of interleukin-5 (IL-5), tumor necrosis factor-α (TNF-α), NOx metabolites, and allergen-specific immunoglobulin E (sIgE) scores. A total of 112 patients with acute bronchial asthma (57 males and 55 females) aged 3.2–9.5 years (median 6) were investigated. Ageand gender-matched healthy subjects (n = 25) were evaluated as a control group, who had no evidence of allergic diseases and atopic sensitization based on skin-prick test results. Received: January 9, 2013 Accepted after revision: February 17, 2013 Published online: July 11, 2013

Interpretation of food specific immunoglobulin E levels in the context of total IgE

BackgroundFood specific immunoglobulin E (IgE) (fsIgE) cut points are used in the evaluation of food allergies. Concomitant measurement of total IgE (tIgE) is traditionally not obtained. We anecdotally observed elevations in fsIgE mirroring tIgE increases, which may confound accurate interpretation. ObjectiveTo determine whether changes in tIgE were associated with fsIgE and whether predictions of fsIgE could be formulated based on tIgE. MethodsWe studied children younger than 18 years who had both tIgE and fsIgE (egg, n = 136; milk, n = 123; peanut, n = 201; soy, n = 55) obtained simultaneously on 1 or more occasion between January 2008 and February 2011. After institutional review board approval, natural log-transformed (ln) tIgE and fsIgE levels were analyzed using univariate and multivariate regression models to assess associations and predict fsIgE using tIgE and other covariates. ResultsSoy IgE levels were strongly correlated (ρ = 0.85, P < .001), whereas egg, milk, and peanut IgE levels were substantially correlated (ρ = 0.69, 0.69, and 0.66, respectively, P < .001) with tIgE. A 1-unit increase in ln(tIgE) was significantly correlated with unit increases in ln(egg IgE) (0.77), ln(milk IgE) (0.84), ln(peanut IgE) (0.87), and ln(soy IgE) (0.89) (P < .001). The ln(tIgE)-based univariate models could predict fsIgE in the validation data with strong (soy) and substantial (egg, milk, and peanut) predictive ability (P < .001). ConclusionOur study found significant and parallel relationships between tIgE and fsIgE levels to egg, milk, peanut, and soy. It underscores the importance of examining fsIgE levels in context of tIgE while making diagnostic and management decisions in children with food allergies.

African Ancestry is a Risk Factor for Asthma and High Total IgE Levels in African Admixed Populations

Characterization of genetic admixture of populations in the Americas and the Caribbean is of interest for anthropological, epidemiological, and historical reasons. Asthma has a higher prevalence and is more severe in populations with a high African component. Association of African ancestry with asthma has been demonstrated. We estimated admixture proportions of samples from six trihybrid populations of African descent and determined the relationship between African ancestry and asthma and total serum IgE levels (tIgE). We genotyped 237 ancestry informative markers in asthmatics and nonasthmatic controls from Barbados (190/277), Jamaica (177/529), Brazil (40/220), Colombia (508/625), African Americans from New York (207/171), and African Americans from Baltimore/Washington, D.C. (625/757). We estimated individual ancestries and evaluated genetic stratification using Structure and principal component analysis. Association of African ancestry and asthma and tIgE was evaluated by regression analysis. Mean ± SD African ancestry ranged from 0.76 ± 0.10 among Barbadians to 0.33 ± 0.13 in Colombians. The European component varied from 0.14 ± 0.05 among Jamaicans and Barbadians to 0.26 ± 0.08 among Colombians. African ancestry was associated with risk for asthma in Colombians (odds ratio (OR) = 4.5, P = 0.001) Brazilians (OR = 136.5, P = 0.003), and African Americans of New York (OR: 4.7; P = 0.040). African ancestry was also associated with higher tIgE levels among Colombians (β = 1.3, P = 0.04), Barbadians (β = 3.8, P = 0.03), and Brazilians (β = 1.6, P = 0.03). Our findings indicate that African ancestry can account for, at least in part, the association between asthma and its associated trait, tIgE levels.

Diagnostic Agreement of Different IgE Assay Methods, Immunocap and ‘Extended Range' Immulite 2000 3gAllergy in Japanese School Age Children

S U N D A Y 417 Diagnostic Agreement of Different IgE Assay Methods, Immunocap and Extended Range' Immulite 2000 3gAllergy in Japanese School Age Children Mari Kondo, Mayumi Sugimoto, MD, Keigo Kainuma, MD, Reiko Tokuda, Mizuho Nagao, MD, Takao Fujisawa, MD, FAAAAI; Mie National Hospital, Tsu, Japan, Mie National Hospital, Mie National Hospital, Mie, Japan. RATIONALE: Quantitative measures of allergen specific IgEantibody (sIgE) using different methods, IMMULITE 2000 3gAllergy (3g) and ImmunoCAP (CAP) assays, have to be interchangeable. Recently, extended measurement range of 3g, 0.1 ‘500IUA/mL, has been evaluated in Japan. METHODS: Serum samples were collected from 144 healthy and allergic children as classified by the ISAAC questionnaire. Samples were tested for total IgE (tIgE) and allergen specific IgE (sIgE) to house dust mite (HDM), Japanese cedar pollen (JCP), egg white and milk using both 3g and CAPassays. RESULTS: tIgE levels for CAP & 3g were almost identical.sIgE levels to various allergens by the two assays were highly correlated with Spearman’s r of >0.9. Values with the 3g assay tended to be higher than those by CAP, possibly a result of the wider 3greportable range. The area under the curve (AUC) determined from analysis of allergic and nonallergic groups were nearly identical between the assays for tIgE, sIgE for HDM and JCP, resulting in similar sensitivity and specificity calculations. Also in both methods, increasing sIgEto HDM correlated with a higher number of co-morbid allergic diseases. In particular, 3gshowed a greater significant difference because of the wider measurement range. CONCLUSIONS: sIgE levels to inhalant and food allergens measured by the 3g and CAP systems are highly correlated. The extended measurement range of the 3g assay may provide additional information for early detection of sensitization and monitoring of highly sensitized patients.

The prevalence and risk factors of allergic and respiratory symptoms in a regional cohort of extremely low birth weight children (&lt;1000 g)

BackgroundChildren who were <1000 g (ELBW extremely low birth weight) at birth more frequently present with wheezing which is the most common reason that pediatric consultation is sought. Therefore asthma is diagnosed very often. However is the asthma that is diagnosed in ELBW subjects atopic in origin, or is there a different etiology?AimTo determine if ELBW infants are at higher risk for the development of allergic and respiratory symptoms and to establish if there were any specific risk factors for these symptoms.Methods81 children born with a mean birthweight of 845 g (91% of available cohort) were evaluated at the mean age 6.7 years. The control group included 40 full-term children. The children were examined for clinical signs of allergy, and were subjected to the following tests: serum total IgE, skin prick tests (SPT), exhaled nitric oxide measurement (FeNO) and spirometry.ResultsELBW children had wheezing episodes more often (64% vs. 25%; OR (odds ratio): 5.38; 95% CI (confidence interval): 2.14-13.8) and were diagnosed more frequently with asthma (32% vs. 7.5%; OR: 5.83, 95% CI: 1.52-26) than their term born peers. The most important risk factors for wheezing persistence were hospitalization and wheezing episodes in first 24 months of life. Mean serum tIgE level (geometric mean: 32+/−4 vs. 56+/−4 kU/L; p=0.002) was higher and the number of children with positive results of tIgE level (12% vs. 32%; p=0.02) were more frequent in the control group. Children from the control group also more frequently had SPT, however this data was not statistically significant (11% vs. 24%; p=0.09). All of the ELBW had normal FeNO level (<=20 ppb), but 5 children from the control group had abnormal results (p=0.02). There was no difference between the groups in the occurrence of allergic symptoms.ConclusionELBW children have more frequent respiratory, but not allergic problems at the age of 6–7 years compared to children born at term. The need for rehospitalization in the first 2 years of life, was a more important risk factor of future respiratory problems at the age of 7 than perinatal factors, the diagnosis of bronchopulmonary dysplasia or allergy.