IgE antibody in the serum--detection and diagnostic significance.

Sensitization of human airways: what is the role of immunoglobulin-E?

Extensive IgE serology in occupational or environmental health studies is often hampered by a lack of technical facilities and finance. The use in population studies of relatively simple and inexpensive enzyme immunoassays (EIAs) was therefore evaluated for the assessment of total serum immunoglobulin E (IgE), and of specific IgE reactions with various common (house dust mites, grass and birch pollen, and cat) or occupational (fungal alpha-amylase and rat urinary protein) allergens. Total IgE was measured with a sandwich EIA, calibrated with commercially available IgE standards. Reproducibility was studied by testing pooled normal human serum samples in each of a large series of test plates. A panel of 156 children's serum samples with known IgE values was used to compare the assay with other total IgE assays. A previously developed EIA for anti-yeast IgE was adapted for the measurement of IgE reacting with various common and occupational allergens. Binding of IgE to microwells coated with commercially available allergen extracts, or allergen preparations from our own laboratory, was measured with a monoclonal anti-human IgE antibody and subsequent incubations with biotinylated rabbit anti-mouse Ig and avidin-peroxidase. Panels of serum samples from school children (n = 116), bakery workers (n = 126), and laboratory animal workers (n = 52) were used to study sensitivity and specificity, with reference to skin prick tests as the standard, and to compare the EIAs with commercially available test kits. The detection limit of the EIA for total IgE was 0.5-1 kU/l for undiluted serum samples, and the coefficient of variation between assays was less than 15% at serum concentrations between 1 and 150 kU/l. Results obtained with the panel of 156 children's serum samples were strongly correlated (r2 = 0.86) with IgE concentrations measured previously by radioimmunoassay. The results of the EIA for various occupational allergens correlated very well, both qualitatively and quantitatively, with the results of commercial test kits. Sensitivity and specificity of the EIA results as a predictor of skin prick test reactivity towards common allergens (house dust mite, grass pollen, birch pollen, and cat) were remarkably high (> 80%-90%) in the series of 116 children's serum samples. In a population of bakery workers the specificity of the EIAs was also very high (> 90%). The sensitivity was notably lower (30%-70%) in this adult population, which is, however, in agreement with results reported for conventional IgE tests. As the costs were estimated to be at least five to 10-fold lower than those of commercial test kits, the EIAs for total and specific IgE may be very useful tools in epidemiological studies of atopic respiratory or other disorders.

Eosinophil count, serum CCL17/18/26 and immunoglobulin E levels in atopic dermatitis: upadacitinib phase 2 study analysis

The importance of IgE in airway inflammation and development of AHR in allergen-sensitized mice has been compared and contrasted in different models of sensitization and challenge. Using different modes of sensitization in normal and genetically manipulated mice after anti-IgE treatment, we have been able to distinguish the role of IgE under these different conditions. Striking differences in the three sensitization protocols were delineated in terms of the role of allergen-specific IgE, extent of eosinophilic airway inflammation, and development of AHR (Table 1). The highest levels of IgE and eosinophil infiltration (approximately 20-fold increases) were achieved after systemic sensitization with allergen (plus adjuvant) followed by repeated airway challenge. Passive sensitization with allergen-specific IgE followed by limited airway challenge induced a modest eosinophilic inflammatory response in the airways despite high levels of serum IgE. Exposure to allergen exclusively via the airways also resulted in a modest serum IgE response and a limited eosinophilic inflammatory response (approximately fourfold increases). Under all of these conditions, inhibition of IL-5-mediated eosinophilic airway inflammation was associated with attenuation of AHR. In contrast, the differences in the responses to the different modes of allergen exposure were associated with differences in the requirements for IgE in the development of AHR (Table 1). In the two models associated with mild eosinophil infiltration (passive sensitization and exclusive airway exposure), IgE was required for the development of AHR but did not substantially enhance airway inflammation on its own. However, IgE-allergen interaction was able to enhance T-cell function in vitro and induce T-cell expansion in vivo. In mice systemically sensitized and challenged via the airways, IgE (or IgE-mediated mast-cell activation) was not required for T-cell activation, eosinophilic inflammation and activation in the airways, or development of AHR. This was most clearly seen in B-cell-deficient and mast-cell-deficient, low-IgE-responder mouse strains (B6, B10) and in anti-IgE-treated high-IgEresponder mice (BALB/c). At the same time, we confirmed the importance of IgE in the induction of immediate-type hypersensitivity (mast-cell activation, immediate cutaneous hypersensitivity, passive cutaneous and systemic anaphylaxis). These differences were also highlighted by the means used to detect altered airway function. Passive sensitization and limited airway challenge or exclusive airway exposure to allergen over 10 days elicited changes in airway function that could be detected only in tracheal smooth-muscle preparations exposed to EFS. In contrast, systemic sensitization followed by repeated airway challenge resulted not only in changes in the contractile response to EFS but also in increased responsiveness to inhaled MCh. Thus, these results distinguish not only the differential involvement of IgE and eosinophil numbers but also their contribution to the readouts used to monitor airway function. Based on these studies, we conclude that IgE plays an important role in the development of airway inflammation and AHR under conditions in which limited IL-5-mediated eosinophilic airway infiltration is induced. In conditions where a robust eosinophilic inflammation of the airways is elicited, IgE (and IgE-mediated mast-cell activation) does not appear to be essential for airway inflammation and the development of AHR, detected as increased responsiveness to inhaled MCh. These findings reveal the potential importance of differential targeting in the treatment of allergic diseases with a predominance of IgE-mediated symptoms, e.g., allergic rhinitis and conjunctivitis, where anti-IgE may be an effective therapy, compared to those diseases with a predominant inflammatory component, e.g., AHR in atopic bronchial asthma, where anti-inflammatory or anti-IL-5 therapy may be more beneficial.

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

In this study we aimed to assess whether the association between asthma (defined by symptoms and bronchial responsiveness) and total immunoglobulin E (IgE) levels was independent of specific IgE levels to common aeroallergens. A general population-based sample, supplemented with symptomatic individuals, comprising 1,916 young adults, aged 20-44 years, from five areas of Spain, performed a face-to-face respiratory questionnaire, and spirometry, and had total and specific serum IgE levels to mites, pets and moulds recorded. In 1,626 of the subjects, a dose-response methacholine challenge test was completed. Subjects reporting current attacks of asthma showed an association with total IgE (odds ratio (OR) for IgE > 100 kU.L-1 = 4.73, 95% confidence intervals (95% CI) = 2.01-11.12, adjusted for specific IgE, sex, age, smoking, forced expiratory volume in one second (FEV1), and area), which did not vary by bronchial responsiveness. The association between total IgE and asthma also occurred among those with negative specific IgE antibodies (OR 18.0; 95% CI 13.9-120). Individuals with current wheezing and bronchial responsiveness without attacks of asthma also showed an adjusted association with total IgE (OR 4.96; 95% CI 2.32-10.6), which remained for persons without specific IgE (OR 5.86; 95% CI 2.18-1.7). These findings reinforce previous evidence that asthma is associated with increased levels of total IgE, even in subjects negative for specific IgE to common aeroallergens.

Immunoglobulin E and allergy.

Immunoglobulin E (IgE) has been identified on macrophage-like cells in the villi of human placenta, irrespective of the serum IgE levels or allergy status of the mother. The origin of placental IgE is debated and it is not known if it is spontaneously produced, so-called 'natural IgE', or if it has any specificity for certain allergens. The aim of this study was to investigate if placental IgE originates from mother or child and to analyse its specificity. Immunoglobulin E was eluted from placenta by lowering the pH. Total and allergen-specific IgEs were measured in placenta eluate, maternal and cord blood plasma by means of ImmunoCAP (Phadia AB). The levels of natural antibodies were determined with an anti-phosphorylcholine (PC) enzyme-linked immunosorbent assay, as natural IgE has been shown in one previous publication with this assay. Detectable amounts of IgE were eluted from 11/12 full-term placentas. Natural (anti-PC) IgE antibodies were detected in low amounts in maternal plasma but not in the placental eluate or in cord blood plasma. There was a significant correlation between the amount of total IgE eluted from placenta and the levels of total IgE in maternal plasma; however, not between maternal and cord blood plasma. Allergen-specific IgE was only found in placental eluates from mothers with specific IgE towards these allergens. Furthermore, there was a significant correlation between the amount of allergen-specific IgE eluted from placenta and the levels of allergen-specific IgE in maternal plasma. Allergen-specific IgE could not be detected in cord blood. These results suggest a maternal origin of placental IgE, which can be allergen-specific.

A new commercial immunochromatographic test (Allerwatch) has recently been developed for determining total immunoglobulin E (IgE). We previously reported on the use of this kit for analyzing tear fluid samples collected during the spring. In this study, we examined the relationship between the total IgE level in tears and the specific serum IgE levels in patients with autumnal allergic conjunctivitis. A prospective, nonrandomized cross-sectional study was conducted in 36 patients with autumnal allergic conjunctivitis (autumnal allergic group), in 32 age-matched and sex-matched healthy control subjects (control group), and in 10 patients with epidemic keratoconjunctivitis. Total tear IgE score was determined in all subjects using the Allerwatch test (0, 1, and 2), whereas the serum levels of total IgE and specific IgE for 12 inhaled allergens were measured using the Phadezym PRIST and CAP-RAST systems, respectively. Positivity rates for total tear IgE were significantly higher in the autumnal allergic group as compared with the control and epidemic keratoconjunctivitis groups (88.9% vs. 0.0% vs. 0.0%, P < 0.00001). In the autumnal allergic group, there was a significant correlation between the total tear IgE score and the log-transformed total serum IgE level (r = 0.84). Significant correlations were also seen with the IgE serum levels for Dermatophagoides pteronyssinus (r = 0.53), house dust (r = 0.51), acarus (r = 0.49), cedar pollen (r = 0.33), and mugwort (r = 0.33). Multivariate logistic regression analysis showed that the only significant predictor of the total tear IgE score was the log-transformed total serum IgE level (odds ratio = 2.76, P < 0.00001). The correlation between the Allerwatch total tear IgE score and the specific IgE serum levels against house dust mites suggests that house dust mite allergens might be the primary cause of allergic conjunctivitis during autumn in Japan. The Allerwatch methodology can provide rapid measurements of total IgE in the tear fluid, which makes it possible to easily diagnose allergic conjunctivitis in an outpatient setting.

Isotype-specific agglutination-PCR (ISAP): A sensitive and multiplex method for measuring allergen-specific IgE

Serum levels of total immunoglobulin E (IgE) and allergen-specific IgE are related to asthma severity and risk factors for persistent asthma in childhood wheezing. Inhaled corticosteroids (ICS) have been the most effective therapy in children with asthma, as well as in adults. The serum levels of total and mite specific IgE in children with asthma and the effects on IgE levels of beclomethasone dipropionate (BDP) treatment on IgE levels in asthmatic children were investigated. First, a cross-sectional study of 255 children with asthma was carried out to measure IgE levels. Children under three years of age with asthma who were negative for Df-specific IgE were then treated with BDP or disodium cromoglycate (DSCG) as controls for one year. Serum IgE levels, numbers of eosinophils in peripheral blood and clinical variables were determined before and after treatment. After one-year DSCG treatment, the total IgE levels increased significantly, whereas the levels remained the same during BDP treatment. Five of 22 (23%) patients in the DSCG-treated group became positive for Df-specific IgE; however, only one of 13 (8%) in the BDP-treated group became positive. Taken together, ICS therapy may modulate the levels of total IgE and allergen-specific IgE.

A genetic basis for asthma- and atopy-related quantitative traits, such as allergen-specific immunoglobulin E (IgE) levels, has been suggested by the observed familial aggregation of these traits in temperate climates. Less information is available for tropical climates, where different allergens may predominate. Sensitivity to the mite Blomia tropicalis is related to asthma in tropical climates, but heritability of B. tropicalis sensitivity and the impact of age, sex, and other environmental covariates on heritability have not been widely explored. Total and specific IgE levels were measured by immunochemiluminescent assay in 481 members of 29 Barbadian families (comprised of 340 parent-offspring trios or pairs) ascertained through two asthmatic siblings. Trait heritability was estimated using regression of offspring on mid-parent (ROMP) and pairwise correlation analysis of unadjusted IgE levels and on residual values after adjustment for covariates. Heritability of IgE levels to the major antigen of B. tropicalis (Blo t M) estimated by ROMP in 180 complete parent-offspring trios was 0.56. Heritability was consistently greater for male offspring than for female offspring. Similar sex-specific patterns were observed for specific IgE to Dermatophagoides pteronyssinus and total IgE levels and were relatively unaffected by adjustment for covariates. Pairwise correlational analyses of specific and total IgE levels showed similar results. Moderate heritability of Blo t M IgE levels was detected in these Barbadian families and was greater for sons than daughters. Adjustment for covariates had minimal impact. This suggests that future investigations of genetic determinants of IgE levels should include approaches that allow for potential sex differences in their expression.

Asthma, allergy, and IgE levels in NYC head start children

Type I allergy is an immunoglobulin E (IgE)-mediated hypersensitivity disease inflicting more than quarter of the world population. In order to identify allergen sources, skin provocation test and IgE serology was performed using allergen extracts. Such process identifies allergen-containing sources but cannot identify the disease-eliciting allergenic molecules. Recently, microarray technology has been developed for allergen-specific IgE detection using rolling circle amplification. This study was carried out to evaluate protein chip technology for the quantitative measurement and limits of sensitivity of multiple allergen-specific IgE by an immunofluorescence assay. Significance of positive calibrators was tested using purified human IgE. Dermatophagoides pteronyssinus (Dp), egg white, milk, soybean, and wheat were used as allergens and human serum albumin as negative control. Sensitivity and clinical efficacy of protein chip were evaluated using allergy immune serum for Dp. The fluorescent intensities for purified human IgE as calibrator were well correlated with the concentrations of human IgE. Two-fold dilution of serum allowed an optimal reaction with Dp (1 mg/ml) at which serum Dp-specific IgE levels by protein chip were compatible with those by UniCap. The sensitivity of protein chip in this study was found at level of 1 IU/ml of IgE. Dp-specific IgE levels by protein chip correlated well with those of UniCap by comparing 10 atopic dermatitis. Additional 18 sera were tested for above multiple antigens other than Dp and significant results were obtained for many antigens as well as Dp. These results indicated that spotting of heterogeneous protein mixture on protein chip and the quantitative measurement of serum allergen-specific IgE levels using immunofluorescence assay can be successfully applied in the clinical laboratory for the diagnosis of allergy and could be applied to diagnosis of autoimmune and infectious diseases

Chapter 56 - Allergic Diseases