Total Immunoglobulin E Concentrations Research Articles

Reference Values and Utility of Serum Total Immunoglobulin E for Predicting Atopy and Allergic Diseases in Korean Schoolchildren.

The present study aimed to investigate the distribution of total serum immunoglobulin E (IgE) levels in Korean schoolchildren and to evaluate its utility in the prediction of atopy and allergic diseases. A nationwide, cross-sectional survey was conducted in first grade students from randomly selected elementary and middle schools. Total IgE levels were measured by ImmunoCAP. Skin prick tests were performed for 18 common inhalant allergens to determine the presence of atopy. Children aged 12–13 years and parents of children aged 6–7 years were asked to complete questionnaire assessing allergic diseases. The cut-off levels of total IgE were determined by analyzing receiver operating characteristic curves. The median total IgE level was 86.7 kU/L (range: 1.5–4,523.1) in 3,753 children aged 6–7 years and 94.7 kU/L (range: 1.5–3,000.0) in 3,930 children aged 12–13 years. Total IgE concentrations were higher in children with atopy or allergic diseases than in those without (all P < 0.001). At the cut-off value of 127.7 kU/L, sensitivity, specificity, and positive and negative predictive values (PPV and NPV) were 67.1%, 75.4%, 65.4%, and 76.7%, respectively, in elementary schoolchildren. At the cut-off value of 63.0 kU/L, sensitivity, specificity, PPV, and NPV were 81.9%, 66.6%, 75.0%, and 75.1%, respectively, in middle schoolchildren. PPV and NPV were ≥ 70% when cut-offs of 258.8 kU/L and 38.4 kU/L were used for the diagnosis of atopy in 6–7 year-olds and 12–13 year-olds, respectively. This nationwide population-based study provided the first normal reference ranges of total IgE in Korean schoolchildren.

Revision of omalizumab dosing table for dosing every 4 instead of 2 weeks for specific ranges of bodyweight and baseline IgE

The dosing level and frequency of omalizumab are guided by a dosing table based on total serum immunoglobulin E (IgE) and bodyweight. Using a validated, mathematical simulation model (based on concentration data from 8 studies), we evaluated the impact of a revised omalizumab dosing table (every 4weeks dosing regimen) on the pharmacokinetic and pharmacodynamic profiles of free and total IgE. Safety analysis, in patients with high levels of exposure to omalizumab, was done using data from the clinical and post-marketing databases. The model accurately predicted observed omalizumab, free and total IgE concentrations. After reaching steady-state, the average increase in exposure was 10%, even for patients with the highest concentrations at the upper 97.5th percentile. Free IgE suppression slightly increased in the initial phase, and slightly reduced at the trough of the dosing cycle, but average suppression remained similar for both regimens. The safety profile of omalizumab was similar for patients receiving higher or lower doses. Thus, doubling the dose of omalizumab, in a subset of patients receiving 225–300mg of omalizumab (every 2weeks dosing regimen) can efficiently suppress free IgE without compromising safety or efficacy.

Are higher serum IgE concentrations associated with adult cardiovascular disease?

The burden of cardiovascular disease (CVD) is high and likely to increase in future decades as a result of demographic and epidemiological transitions in populations. In the United States, CVD is responsible for 17% of national health expenditures. As the population ages, these costs are expected to continue to increase substantially [1]. Continuous identification of novel risk and protective contributors will play an important role in preventing and delaying the disease and therefore saving costs at all levels and prolonging life expectancy. Previous research studies have suggested that IgE-mediated events may play a role in the pathogenesis of CVD, involving platelet activation and arterial spasm [3]. In this context, it was aimed to determine the relationships between serum total and allergen-specific immunoglobulin E (IgE) and risk of CVD in a national population-based setting. As described elsewhere [2], United States National Health and Nutrition Examination Surveys is a national, population-based, multiyear, cross-sectional study. Information on demographics, lifestyle factors, and medical conditions including self-reported CVD with ever coronary heart disease, stroke, heart failure, heart attack, and anginawas obtainedbyhousehold interviewusingquestionnaires.Written informed consent was obtained for all subjects. In the 2005–2006 cohort, participants aged 1 year and older were tested for serum total IgE concentrations and people aged 6 and above were tested for additional allergen-specific IgE concentrations using the Pharmacia Diagnostics ImmunoCAP 1000 System (Kalamazoo,Michigan). A detailed description of the laboratorymethod can be found at NHANES 2005–2006web page (http://www.cdc.gov/nchs/data/nhanes/nhanes_05_06/al_ige_d.pdf). Since people aged 20 and over were asked in relation to cardiovascular disease conditions, participants aged 20 and above were eligible to be included in the current analysis. Effects of serum total (cutoff: 170 kU/L) and 19 allergen-specific (cutoff: 0.35 kU/L) IgE concentrations on risk of CVD were examined by t-test, generalized linear model, and logistic regression model, with Pb0.05 considered statistically significant. Total CVD was counted as having any of subtypes (binary: categorical variable) and was summed by all subtypes as number of CVD events (continuous variable). Covariates included age, sex, ethnicity, education (cutoff: high school), body mass index, high blood pressure (≥140 mm Hg for systolic blood pressure and ≥90 mm Hg for diastolic blood pressure), active smoking (cotinine as a proxy), serum insulin, serum LDL-cholesterol, and alcohol consumption (≥12 drinks in a year). Final models were also weighted. Statistical software STATAversion 12.0 (STATA, College Station, Texas, USA) was used to perform all the analyses. Since this study is secondary data analysis by extracting data from the NHANES website, no further ethics approval is required. Table 1 presents the characteristics of included participants (N=4979). Table 2 shows the effects of serum total IgE concentrations on the risk of CVD by subtypes. Apparently, people with any CVD type had higher levels of serum total IgE concentrations. In the multi-level regression modeling after full adjustments and being weighted, people with higher serum total IgE concentrationswere likely to have coronary heart disease (OR 2.02, 95%CI 1.001–4.08, P=0.05). Moreover, among all allergen-specific IgE concentrations, only serum shrimp IgE antibody was significantly associatedwith coronary heart disease (OR 2.96, 95%CI 1.06–8.28, P=0.04). However, serum shrimp antibody was not significantly associated with other CVD subtypes (Table 3). Although number of CVD events seemed to be related to higher serum shrimp IgE antibody, it did not reach significance. In the present study, the effects of serum total and seafood-specific IgE concentrations on risk of CVD subtypes and number of events were firstly examined in a national and population-based setting. It was observed that serum total IgE concentrations and serum shrimp IgE antibodywere significantlyassociatedwith an increased riskof coronary

The Essential Role of Anti-Thyroid Antibodies in Chronic Idiopathic Urticaria

Background. An autoimmune etiology has been suggested in up to one-third of cases of chronic idiopathic urticaria (CIU), in which it has been proposed that a subset of cases are associated with thyroid autoimmunity. The objective of our present study was to verify the prevalence of thyroid antibodies in the patients with CIU. Methods. Sixty patients aged 12–51 years, who met criteria for CIU, and 40 aged-matched healthy controls (18 males and 22 females) were participated in this study. Serum anti-thyroid antibodies (ATAs), thyroid hormones, total immunoglobulin E (IgE), and food allergen-specific IgE antibodies were measured. The CIU group was treated with anti-H1 and anti-H2 histamines for 3 weeks. Results. The total ATA positive rate was 27.3% (33% males and 25% females) in the CIU group. The prevalence of anti-thyroglobulin antibodies, anti-TSH-receptor antibodies, and anti-thyroid peroxidase antibodies were 16.6%, 83.3%, and 8.3%, respectively. The thyroid hormones, T3, and T4, and the TSH were within the normal limits. The radioallergosorbent test was negative for food allergens, and only 18% of the patients had a total IgE concentration >200 IU/mL. Conclusion. ATAs were found in 27% of the patients with CIU, but these antibodies did not dysregulate thyroid hormone secretion nor did they mediate any clinical manifestations.

Relationships between total and allergen-specific serum IgE concentrations and lung function in young adults

BackgroundPrior studies have shown relationships between serum immunoglobulin E (IgE) and asthma. ObjectiveTo investigate relationships between total and allergen-specific IgE concentrations and lung function in young adults. MethodsMeasurements of total IgE, allergen-specific IgE to 6 common allergens, and spirometry (forced expiratory volume in one second [FEV1], forced vital capacity [FVC], FEV1/FVC, and percent change in FEV1 after bronchodilation) were used to calculate correlations between the logarithmically transformed IgE values and measures of lung function among participants in a birth cohort not selected for risk of allergic disease stratified by current asthma, prior asthma, or no asthma. ResultsThe 428 participants were 51.6% female, 93% white, and 18.4 (standard deviation = 0.6) years old. Forty-eight (11.2%) had current asthma, 55 (12.9%) had a history of asthma, and 325 (75.9%) never had asthma. For males with current asthma, correlations between total IgE and FEV1% and FVC% were −0.51 (P = .06) and −0.70 (P = .005), respectively. For females with current asthma, the only significant correlation was between total IgE and the FEV1/FVC ratio (−0.55, P = .001). After excluding smokers and individuals without detectable allergen-specific IgE, the negative correlations for both males and females remained statistically significant. The correlations among males or females with prior asthma or no history of asthma were minimal and not statistically significant. The sum of the allergen-specific IgEs showed the same pattern of relationships to lung function as did total IgE. ConclusionOur results show significant negative correlations that vary by gender between both total and allergen-specific IgE and measurements of lung function in young adults with current asthma.

SICAM-1 and TNF-α in Asthma and Rhinitis: Relationship with the Presence of Atopy

Background. A genetically determined overproduction of specific immunoglobulin E (IgE) underlies many diseases like asthma or allergic rhinitis. IgE as well as tumor necrosis factor-α (TNF-α), and intercellular adhesion molecule-1 (ICAM-1) play a critical role in the induction and maintenance of inflammation. While the correlation between IgE and atopy is inseparable, little is known about the correlation of atopy with markers of inflammation. Objective. We investigated the relationship between the serum concentrations of TNF-α, soluble ICAM-1 (sICAM-1), and the presence of atopy in patients with persistent rhinitis or asthma. Methods. Serum concentrations of sICAM-1, TNF-α, and total IgE were investigated in 64 adults with persistent allergic rhinitis, 17 subjects with nonatopic rhinitis, 90 patients with asthma, and 21 healthy individuals. Atopy was diagnosed on the basis of positive family history, skin prick tests, and serum IgE concentration. Results. Total IgE concentration was significantly higher in patients with atopic rhinitis or asthma when compared with nonatopic patients and healthy individuals and was the highest in patients suffering from severe atopic asthma who were not treated with systemic glucocorticosteroids. Although there were marked alterations in IgE in atopic and nonatopic patients, there were no significant differences between atopic and corresponding groups of nonatopic rhinitic and asthmatic patients in sICAM-1 and TNF-α concentrations. (sICAM-1 in rhinitis: atopic vs. nonatopic patients: 224.02 and 221.08 ng/ml, respectively, p > .05; in mild/moderate asthma: atopic vs. nonatopic: 306.22 and 326.39 ng/ml, respectively, p > .05; severe asthma without oral corticosteroids therapy: atopic vs. nonatopic: 418.03 and 468.09 ng/ml, respectively, p > .05; and severe asthma with oral corticosteroids therapy: atopic vs. nonatopic: 320.66 and 308.09 ng/ml, respectively, p > .05). Conclusions. Concentrations of sICAM-1 and TNF-α are significantly higher in patients with asthma compared with those observed in patients with rhinitis, but they are independent of the presence of atopy.

Spondylarthritis presenting with an allergic immediate systemic reaction to adalimumab in a woman: a case report

IntroductionThe efficacy of adalimumab, a fully human anti-tumor necrosis factor α recombinant antibody, has dramatically improved the quality of life of patients with rheumatoid and psoriatic arthritis and Crohn's disease. Because it is fully human, one should not expect immune reactions to this molecule. Adverse reactions to adalimumab are limited mainly to injection site reactions and are very common. Immediate systemic reactions are rarely reported.Case presentationWe report the case of a 61-year-old Caucasian woman who was treated with adalimumab for spondylarthritis and developed injection site reactions after the sixth dose. After a two-month suspension, she recommenced therapy and experienced two systemic reactions. The first occurred after one hour with itching of the palms and soles and angioedema of the tongue and lips. Thirty minutes after the next dose the patient had itching of the palms and soles with diffusion to her whole body, angioedema of the lips, dizziness and visual disturbances. A skin-prick test and intra-dermal tests with adalimumab gave strong positive results at the immediate reading. However, serum-specific immunoglobulin E (IgE) to adalimumab were not detectable by using Phadia solid phase, especially harvested for this case, in collaboration with our Immunology and Allergy Laboratory Unit. Her total IgE concentration was 6.4 kU/L.ConclusionWe describe what is, to the best of our knowledge, the first reported case of immediate systemic reaction to adalimumab studied with a skin test giving positive results and a serum-specific IgE assay giving negative results. The mechanism of the reaction must be immunologic but not IgE-mediated.

Feline-specific serum total IgE quantitation in normal, asthmatic and parasitized cats

Immunoglobulin E (IgE) plays an important role in defense against parasitic infections as well as allergy. Knowledge of serum total IgE concentrations may have value in diagnosis and prognostication of various disorders; however, to date, no studies have reported feline serum total IgE concentrations. We hypothesize that serum total IgE concentrations will be greater in spontaneously parasitized and asthmatic cats compared to healthy pet cats. Healthy (n=10), parasitized (10) and asthmatic cats (eight) had measurement of serum total IgE by ELISA. Data were analyzed using a t-test with P<0.05 considered significant. Serum total IgE was higher in parasitized (mean±SEM, 328.4±123.8μg/ml; P<0.028) and asthmatic cats (85.5±19.5μg/ml; P<0.047) compared to healthy cats (45.9±19.6μg/ml). However, serum total IgE had poor discriminatory capability between diseased and healthy cats. In conclusion, this assay can detect small quantities of feline serum total IgE, which may be beneficial in future studies of parasitism or allergic disease.

Allergy and Sensitization during Childhood Associated with Prenatal and Lactational Exposure to Marine Pollutants

BackgroundBreast-feeding may affect the risk of developing allergy during childhood and may also cause exposure to immunotoxicants, such as polychlorinated biphenyls (PCBs), which are of concern as marine pollutants in the Faroe Islands and the Arctic region.ObjectivesThe objective was to assess whether sensitization and development of allergic disease is associated with duration of breast-feeding and prenatal or postnatal exposures to PCBs and methylmercury.MethodsA cohort of 656 singleton births was formed in the Faroe Islands during 1999–2001. Duration of breast-feeding and history of asthma and atopic dermatitis were recorded at clinical examinations at 5 and 7 years of age. PCB and mercury concentrations were determined in blood samples obtained at parturition and at follow-up. Serum from 464 children (71%) at 7 years of age was analyzed for total immunoglobulin E (IgE) and grass-specific IgE.ResultsThe total IgE concentration in serum at 7 years of age was positively associated both with the concomitant serum PCB concentration and with the duration of breast-feeding. However, the effect only of the latter was substantially attenuated in a multivariate analysis. A raised grass-specific IgE concentration compatible with sensitization was positively associated with the duration of breast-feeding and inversely associated with prenatal methylmercury exposure. However, a history of asthma or atopic dermatitis was not associated with the duration of breast-feeding, although children with atopic dermatitis had lower prenatal PCB exposures than did nonallergic children.ConclusionsThese findings suggest that developmental exposure to immunotoxicants may both increase and decrease the risk of allergic disease and that associations between breast-feeding and subsequent allergic disease in children may, at least in part, reflect lactational exposure to immunotoxic food contaminants.

Serum level of immunoglobulin E during pregnancy – does offspring sex matter?

We assessed maternal serum levels of total immunoglobulin E (IgE) in the first, second and third trimester and changes in total IgE levels from first to third trimester in relation to offspring sex. Within a cohort of 29 948 pregnant women, 392 women without a history of pre-eclampsia and with a liveborn child were randomly selected. Information on offspring sex was obtained through linkage to the Medical Birth Registry of Norway. Blood samples from each trimester were analysed for total IgE concentration. Differences in mean levels according to offspring sex were estimated and changes in total IgE levels from first to third trimester were assessed. In all three trimesters there was a tendency of women carrying a male fetus to have a higher mean total IgE level, but significant statistical differences were not reached. The total IgE concentration decreased during pregnancy, but the decrement was less in women carrying a male fetus compared with those who carried a female fetus.

Association of early growth response‐1 gene polymorphisms with total IgE and atopy in asthmatic children

Early growth response-1 (Egr-1) is expressed in human airways and found to modulate tumor necrosis factor, immunoglobulin E (IgE), airway responsiveness, and interleukin-13-induced inflammation in mice. We investigated the effects of Chinese-tagging single nucleotide polymorphisms (SNPs) of Egr-1 on asthma traits in 298 Chinese asthmatic children and 175 controls, and a replication community cohort of 191 controls. Tag SNP (-4071 A-->G) and three additional SNPs (-1427 C-->T, -151 C-->T and IVS1 -42 C-->T) were genotyped by restriction fragment length polymorphism (RFLP). Significant associations were found between plasma total IgE concentration and -4071 A-->G (p = 0.008) and IVS1 -42 C-->T (p = 0.027) in asthmatic patients. After Bonferroni correction, only -4071 A-->G showed significant association. Multivariate regression analysis confirmed this significant association with a standardized coefficient beta of 0.156 (95% CI: 0.046-0.317; p = 0.009) in asthmatics among the three SNPs with age and gender-adjusted. In -4071 A-->G, IgE(log) was significantly higher in patients with the GG genotype than the AA genotype (p = 0.009). In addition, -4071 A-->G was significantly associated with atopy (p = 0.016) and high total IgE concentration (p = 0.030) among asthmatics. Patients with the G allele had a 3.5-fold risk of having atopy and a 2.0-fold risk of having high total IgE concentration than those homozygous for the A allele. This is the first report to show significant association of Egr-1 polymorphisms with plasma total IgE and atopy in asthmatics. It may help to explore the pharmacogenetics of Egr-1 inhibitors.

Decreased Markers of Atopy in Children With Presumed Early Exposure to Allergens, Unhygienic Conditions, and Infections

Stelmach I, Smejda K, Jerzynska J, et al. Ann Allergy Asthma Immunol. 2007;99(2):170–177 PURPOSE OF THE STUDY. To compare 2 populations of children with different risk and protective factors for the development of atopy. STUDY POPULATION. The study group consisted of 415 children living in community foster homes in Lodz, a large industrial city in Poland. The reference group consisted of 500 children who were living with their parents at home and recruited from primary care centers. METHODS. Questionnaires were completed by parents or guardians. The primary outcome measures were skin-prick test results to 14 environmental and 4 food allergens and specific immunoglobulin E (IgE) in serum. Secondary outcomes included symptoms of asthma and allergic diseases, lung function, parental allergy, and family history, including life conditions in early childhood, and markers of allergy, such as total IgE serum concentration and eosinophil blood cell count. Stool samples were analyzed for parasites. RESULTS. The analysis included 408 study children and 402 reference children. Atopy was significantly more prevalent in the reference group (25.9%) than in the foster home children (11.3%). More positive skin-prick test results were observed in children from the reference group than in study children. Specific IgE was significantly higher to dust mites, timothy, and mugworth, as were asthma, rhinitis, and atopic dermatitis, in the reference group. To explain this phenomenon, the investigators selected 16 variables that differed in both groups in the first year of life and related them to atopy. They found that the more cumulative features characteristic of the foster home population (poor living conditions), the lower the risk of atopy. CONCLUSIONS. Extremely unfavorable environmental circumstances, which are characteristic of the foster home population during early childhood, might prevent atopy. REVIEWER COMMENTS. These data may suggest that many of our recommendations to parents (cleaning, reducing mold, prevention of infections) are not protective against development of atopy. The limitation of the study was lack of a search for the mechanism that is protective of atopy for those living in poor conditions. One factor could be endotoxin exposure in old homes, which was the case for 90% of those in foster homes. Furthermore, parasitic infections, prevalent in poor socioeconomic and poor hygienic conditions and further suggested by high eosinophil blood counts and serum total IgE concentrations in the nonatopic foster home children, were not fully evaluated.

Study of gene–gene interactions for endophenotypic quantitative traits in Chinese asthmatic children

Asthma is a complex disease resulting from interactions between multiple genes and environmental factors. Study of gene-gene interactions could provide insight into the pathophysiology of asthma. We investigated the interactions among 18 single-nucleotide polymorphisms in eight candidate genes for plasma total immunoglobulin E (IgE) concentration and peripheral blood (PB) eosinophil count in 298 Chinese asthmatic children and 175 controls. Generalized multifactor dimensionality reduction and generalized linear model were used to analyze gene-gene interactions for the quantitative traits. A significant interaction was found between R130Q in IL13 and I50V in IL4RA for plasma total IgE concentration, with a cross-validation (CV) consistency of nine of 10 and a prediction error of 41.1% (P = 0.013). Plasma total IgE concentration was significantly higher in the high-risk than the low-risk groups (P < 0.0001). For PB eosinophil count, significant interaction was found between C-431T in TARC and RsaI_in2 in FCERIB, with a CV consistency of nine of 10 and a prediction error of 40.2% (P = 0.009). PB eosinophil count was significantly higher in the high-risk group than the low-risk groups (P < 0.0001). Generalized linear model also revealed significant gene-gene interaction for the above two endophenotypes with P = 0.013 for plasma total IgE concentration and P = 0.029 for PB eosinophil count respectively. Our data suggest significant interactions between IL13 and IL4RA for plasma total IgE concentration, and this is the first report to show significant interaction between TARC and FCERIB for PB eosinophil count in Chinese asthmatic children.

A study on serum IgE and clinical symptomatology of atopy in patients suffering from the lysosomal storage disorder Fabry disease

Lysosomal storage disorders may impair intracellular lysosomal processing of antigen with consequences for antibody production [e.g. immunoglobulin E (IgE)] and atopic disease status. Serum concentration of total IgE as well as clinical symptoms of atopic disorders as an indirect consequence of lysosomal impairment of antigen processing were studied in male and female Fabry disease (FD) patients with and without replacement of the missing lysosomal enzyme, alpha-galactosidase A (alpha-Gal A). Observational study in 31 adult FD patients with measurements of total serum IgE concentration. Questionnaire-derived data were obtained for atopic eczema (AE) skin lesions, allergic rhinoconjunctivitis (RCA) and allergic asthma (AA) at present or in the past. Among 12 FD males under enzyme replacement therapy (ERT), 2 showed total IgE concentrations above 100 kU/L. Clinical symptoms for AA were found in 2, RCA and AE in 1, respectively. Among 10 FD females under ERT, 4 showed total IgE concentrations above 100 kU/L. Clinical symptoms for AA were found in 4, RCA in 2 and AE in 2. Among 9 females without ERT, 2 showed total IgE concentrations above 100 kU/L. Clinical symptoms for AA were found in 2, RCA in 2 and AE in none. FD patients may demonstrate an increased total serum IgE concentration and may show symptoms of atopic disorders (AA, RCA, AE) in a prevalence rate comparable to international experience for individuals without FD. There was no difference between patients with and without ERT. Lack of detection of AE in females without ERT is suggested to be caused by the small sample size. FD patients without any alpha-Gal A activity prior to initiation of ERT should be in the focus of future studies.

Oral Administration of Heat-Killed Lactobacillus brevis SBC8803 Ameliorates the Development of Dermatitis and Inhibits Immunoglobulin E Production in Atopic Dermatitis Model NC/Nga Mice

We have previously shown that the oral administration of heat-killed Lactobacillus brevis (L. brevis) SBC8803 strain inhibits IgE production in ovalbumin (OVA)-sensitized BALB/c mice through improvement of the type-1 helper T (Th1)/Th2 balance toward Th1 dominance. Atopic dermatitis is one of the most common skin diseases and is frequently associated with elevated immunoglobulin E (IgE) antibodies against many kinds of allergens. In this study, we investigated the inhibitory effect of oral administration of L. brevis SBC8803 on the development of dermatitis and IgE elevation using the NC/Nga atopic dermatitis model mice. Male 8-week-old NC/Nga mice were sensitized by the topical application of picryl chloride to foot pads and shaved abdomen. These mice were boosted with picryl chloride by topical application onto the ears once a week for 9 weeks. The mice (n=10 per group) were fed a diet containing 0%, 0.05% or 0.5% of heat-killed L. brevis SBC8803 from 2 weeks before the first sensitization to the end of the study. Total IgE concentration in serum, clinical score, and ear thickness were periodically examined throughout the study. Finally, cytokine (interleukin (IL)-4, IL-5, IL-6, IL-10, IL-12, IFN-gamma and transforming growth factor (TGF)-beta) productions from splenocytes and Peyer's patch (PP) cells of mice were measured. Oral administration of L. brevis SBC8803 significantly inhibited IgE production and ear swelling, and suppressed the development of dermatitis in a dose-dependent manner. Immunosuppressive cytokines such as IL-10 and TGF-beta production from PP cells significantly increased in the 0.5% group compared to the control group although Th1-type and Th2-type cytokines production was not affected.

Reduction of the Total IgE Level by Omalizumab in Children and Adolescents

Background: Current data from clinical studies show that patients with severe allergic asthma experience a significant improvement from omalizumab. The early and late allergic reactions are inhibited by formation of complexes with free circulating immunoglobulin E (IgE), independent of which antigen activates the allergic cascade. The dosage of omalizumab depends on body weight and IgE level, yet no parameter has been established to guide dosage changes during therapy. The aim of this study was to investigate the value of the determination of total IgE by ADVIA Centaur assay to monitor the therapy progress. Patients and Methods: Nine patients, 8 to 17 years of age, received therapy with omalizumab due to severe allergic bronchial asthma. In addition, the patients had pronounced rhinoconjunctivitis, food allergy, insect sting allergy, and/or neurodermitis. The total IgE in the serum (Sandwich-Immunoassay ADVIA Centaur) was measured in the patients once monthly before each omalizumab injection as a potential progress parameter. Results: Six months after the beginning of therapy with omalizumab, a significant decrease of the total IgE concentration was found, in comparison to the baseline values (p < 0.01). In all patients, the tolerability of omalizumab was very good; there was a reduction in the frequency of the asthma exacerbations and rescue medications. The dosage of inhaled glucocorticoids could be lowered. All patients reported a clearly improved quality of life. Conclusions: The increase of the total IgE concentrations after administration of omalizumab described in the literature could not be confirmed. The value of total serum IgE as a progress parameter should be investigated in controlled studies with regard to sensitivity and specificity of the respective assays. The establishment of a test procedure for therapeutic monitoring appears urgently necessary, so that the appropriate dosage of omalizumab is applied in children and adolescents. Patients receiving omalizumab therapy should be closely monitored.

Effect of parasitosis on allergic sensitization in rats sensitized with ovalbumin: Interaction between parasitosis and allergic sensitization

Some helminthic infections, especially nematode infections, may behave as allergens and induce allergic sensitization. In this study, the investigators explored whether infections with Syphacia muris and Aspiculuris tetraptera have any effect on the development of allergen-induced cytokine responses and serum total immunoglobulin E (IgE) levels in ovalbumin (OVA)-sensitized rats. Four groups of male Wistar rats were studied. OVA sensitization was generated in 2 groups of rats; the rats in 1 group were infected and those in the other group were not. On day 21 after sensitization, tumor necrosis factor-alpha, interleukin-10, and total IgE levels in serum samples of rats were measured by enzyme-linked immunosorbent assay. The results showed that average concentrations of tumor necrosis factor-a and interleukin-10 were significantly greater in the group of rats infected with parasites and sensitized to OVA compared with the group uninfected with parasites and sensitized to OVA (P=.043 and P=.046, respectively). Upon comparison of total IgE concentrations, the group of rats infected with parasites and given saline solution showed higher levels compared with the group uninfected with parasites and given saline (P=.004). In conclusion, the investigators were unable to show a protective effect of an existing parasitic infection against the development of allergic sensitization upon exposure to OVA.

Clinical significance of serum IgE

Many previous studies have proved that human allergic disease resulted from the formation of antibodies belonging to a unique immunoglobulin isotype termed immunoglobulin E (IgE). Most of IgE- producing plasma cells are found in the lymphoid tissue associated with the gastrointestinal and respiratory tracts. IgE may be found free in the mucosal secretions of these tissues, bound to local mast cells, or distributed by the systemic circulation to mast cells and basophils throughout the body. Total serum IgE concentrations tend to be higher in allergic adults and children compared with non-allergic individuals, but the value of total serum IgE as a screening test for allergic disease is limited. Total serum IgE levels are related to the probability of an individual having detectable allergen-specific IgE. Allergen-specific IgE concentrations vary with a person's age, the degree and duration of the recent allergen or cross-reactive allergen exposure. The value of quantitative assays for allergen-specific IgE has been suggested in recent studies. Serum IgE increases in many non-allergic diseases, including infectious and parasitic diseases. The IgE changes appear to be specific to the infectious agents, whereas non-specific in other diseases. The increased serum IgE in some of these conditions probably results from alterations in immune function. This review summarizes the clinical significance of total and allergen-specific IgE examinations in allergic diseases.

Cytokine gene polymorphisms and atopic disease in two European cohorts. (ECRHS-Basel and SAPALDIA)

BackgroundAtopy and allergic phenotypes are biologically characterized by an imbalanced T helper cell response skewed towards a type 2 (TH2) immune response associated with elevated serum immunoglobulin E (IgE) levels. Polymorphisms in cytokine genes might modulate regulation of the TH1/TH2 balance. We thus aimed at reproducing our previous findings from a European study population on the association of various cytokine polymorphisms with self-reported hay fever as well as increased total and specific IgE levels in two comparable study populations.MethodsTwo prospective Caucasian cohorts were used. In the Basel center of the European Community Respiratory Health Survey (ECRHS, n = 418) ten distinct cytokine polymorphisms of putative functional relevance were genotyped. In the Swiss cohort Study on Air Pollution And Lung Disease In Adults (SAPALDIA, n = 6003) two cytokine polymorphisms were genotyped. The associations of these polymorphisms with atopy were estimated by covariance and logistic regression analysis.ResultsWe confirmed IL4, IL10, IL6 and IL18 as candidate genes for atopic health outcomes. In the large, well-characterized SAPALDIA cohort the IL6(-174G>C) and IL18(-137G>C) polymorphisms were associated with circulating total IgE concentrations in subjects with hay fever. The IL18(-137G>C) polymorphism was also associated with the prevalence of hay fever.ConclusionComprehensive characterization of genetic variation in extended cytokine candidate gene regions is now needed. Large study networks must follow to investigate the association of risk patterns defined by genetic predisposing and environmental risk factors with specific atopic phenotypes.

Anti IgE antibodies for the treatment of difficult asthma

Immunoglobulin E (IgE) is a key factor of allergic reaction and is known to be involved in the immunopathology of asthma. In this review, we discuss the results of trials of a monoclonal antibody (omalizumab) against IgE in patients with allergic asthma. Omalizumab is a humanised murine IgG1 kappa monoclonal antibody which is administered subcutaneously every 2 to 4weeks at a dose calculated according to the patient's body weight and total plasma IgE concentrations. It binds free circulating IgE thus preventing it from binding to high affinity receptors. Omalizumab therapy significantly reduces asthma exacerbations, improves quality of life and has a steroid-sparing effect. It has a good safety profile. This treatment appears to be more effective in the patients with the most severe disease and the worst lung function. Omalizumab therapy is an important novel treatment for difficult-to-control allergic asthma. Because of its systemic mechanism of action, it may be of particular use in patients displaying multiple allergic pathologies. It remains unknown whether the beneficial effects of omalizumab could be extended to patients with severe non allergic (so-called "intrinsic") asthma, a variant of the disease which is often difficult to control.