Low Immunoglobulin E Research Articles

Benralizumab efficacy by atopy status and serum immunoglobulin E for patients with severe, uncontrolled asthma

BackgroundPatients with severe asthma can have eosinophilic inflammation and/or allergen sensitization. Benralizumab is an anti-eosinophilic monoclonal antibody indicated for add-on maintenance treatment of patients with severe asthma aged 12 years and older, and with an eosinophilic phenotype. ObjectiveTo investigate the efficacy of benralizumab by atopic status and serum immunoglobulin E (IgE) concentrations. MethodsWe analyzed pooled results from the SIROCCO (NCT01928771) and CALIMA (NCT01914757) phase III studies. Patients 12 to 75 years old with severe, uncontrolled asthma on high-dosage inhaled corticosteroids plus long-acting β2-agonists received 30 mg of subcutaneous benralizumab every 4 weeks or every 8 weeks (first 3 doses every 4 weeks) or placebo every 4 weeks. The analysis stratified patients who did and did not meet similar omalizumab-qualifying criteria of atopy and serum IgE levels 30 to 700 kU/L. Patients also categorized as having high serum IgE (≥150 kU/L) or low serum IgE (<150 kU/L) and as having atopy or no atopy. Efficacy outcomes were for all patients and by blood eosinophil counts and included annual exacerbation rate ratio and pre-bronchodilator forced expiratory volume in 1 second change at treatment end vs placebo. ResultsBenralizumab every 8 weeks decreased exacerbations by 46% (95% confidence interval 26–61, P = .0002) and increased forced expiratory volume in 1 second by 0.125 L (95% confidence interval 0.018–0.232, P = .0218) vs placebo for patients with at least 300 eosinophils/μL who met the atopy and IgE criteria. For patients with eosinophilia and high or low IgE, treatment with benralizumab every 8 weeks resulted in 42% and 43% decreases in exacerbation rate (P ≤ .0004) and 0.123- and 0.138-L increases in forced expiratory volume in 1 second (P ≤ .0041) vs placebo, respectively. ConclusionBenralizumab treatment decreased exacerbations and improved lung function for patients with severe, uncontrolled eosinophilic asthma regardless of serum IgE concentrations and atopy status.

Lung Function Trajectory Types in Never-Smoking Adults With Asthma: Clinical Features and Inflammatory Patterns.

PurposeAsthma is a heterogeneous disease that responds to medications to varying degrees. Cluster analyses have identified several phenotypes and variables related to fixed airway obstruction; however, few longitudinal studies of lung function have been performed on adult asthmatics. We investigated clinical, demographic, and inflammatory factors related to persistent airflow limitation based on lung function trajectories over 1 year.MethodsSerial post-bronchodilator forced expiratory volume (FEV) 1% values were obtained from 1,679 asthmatics who were followed up every 3 months for 1 year. First, a hierarchical cluster analysis was performed using Ward's method to generate a dendrogram for the optimum number of clusters using the complete post-FEV1 sets from 448 subjects. Then, a trajectory cluster analysis of serial post-FEV1 sets was performed using the k-means clustering for the longitudinal data trajectory method. Next, trajectory clustering for the serial post-FEV1 sets of a total of 1,679 asthmatics was performed after imputation of missing post-FEV1 values using regression methods.ResultsTrajectories 1 and 2 were associated with normal lung function during the study period, and trajectory 3 was associated with a reversal to normal of the moderately decreased baseline FEV1 within 3 months. Trajectories 4 and 5 were associated with severe asthma with a marked reduction in baseline FEV1. However, the FEV1 associated with trajectory 4 was increased at 3 months, whereas the FEV1 associated with trajectory 5 was persistently disturbed over 1 year. Compared with trajectory 4, trajectory 5 was associated with older asthmatics with less atopy, a lower immunoglobulin E (IgE) level, sputum neutrophilia and higher dosages of oral steroids. In contrast, trajectory 4 was associated with higher sputum and blood eosinophil counts and more frequent exacerbations.ConclusionsTrajectory clustering analysis of FEV1 identified 5 distinct types, representing well-preserved to severely decreased FEV1. Persistent airflow obstruction may be related to non-atopy, a low IgE level, and older age accompanied by neutrophilic inflammation and low baseline FEV1 levels.

RAsp f3 and rAsp f4 are associated with bronchiectasis in allergic fungal airways disease

Allergy to thermotolerant filamentous fungi, particularly Aspergillus fumigatus, is closely associated with fixed airflow obstruction, bronchiectasis, and other radiologically defined abnormalities, such as mucus plugging. [1] Woolnough K.F. Richardson M. Newby C. et al. The relationship between biomarkers of fungal allergy and lung damage in asthma. Clin Exp Allergy. 2017; 47: 48-56 Crossref PubMed Scopus (52) Google Scholar However, not all asthma patients who are immunoglobulin E (IgE) sensitized to A fumigatus develop these complications. To identify markers of poor outcomes in fungal allergy with asthma (and cystic fibrosis), the term allergic bronchopulmonary aspergillosis (ABPA) was coined. However, this syndrome was defined largely using criteria that represent a florid immunologic response to A fumigatus rather than clinically relevant outcomes, a problem that remains with the recent modifications recommended by the International Society for Human and Animal Mycology. [2] Woolnough K. Fairs A. Pashley C.H. Wardlaw A.J. Allergic fungal airway disease: pathophysiologic and diagnostic considerations. Curr Opin Pulm Med. 2015; 21: 39-47 Crossref PubMed Scopus (45) Google Scholar Moreover, asthma patients rarely fulfill all criteria for ABPA, whereas fungal allergy in asthma is common, particularly in more severe disease. Denning and colleagues proposed the term severe asthma with fungal sensitization (SAFS), essentially defined as ABPA with a low IgE, to define this larger group. However, not all asthma patients with fungal sensitization have severe disease and not all fungi are associated with lung damage.

Allergic bronchopulmonary aspergillosis in Japan: A nationwide survey

BackgroundAllergic bronchopulmonary aspergillosis (ABPA) is an allergic pulmonary disease characterized by a hypersensitivity reaction to Aspergillus species colonizing the airways. The clinical characteristics of ABPA may differ depending on genetic and environmental background. We performed a nationwide survey to determine the clinical characteristics of ABPA in Japan. MethodsIn 2013, a questionnaire on physician-diagnosed ABPA/allergic bronchopulmonary mycosis was sent to 903 medical centers specializing in respiratory or allergic diseases. Cases fulfilling the following criteria were categorized as possible ABPA-central bronchiectasis (ABPA-CB): 1) presence of specific serum immunoglobulin E (IgE) antibodies or a positive skin reaction to Aspergillus, and 2) bronchiectasis or mucoid impaction in the central bronchi. ResultsOf 499 physician-diagnosed cases reported by 132 clinical centers, 358 cases met the criteria for possible ABPA-CB. Median age of ABPA-CB onset was 57 (interquartile range, 44–68) years; later-onset disease, developing ≥50 years of age, accounted for 66% of the cases and was associated with female sex, delayed onset of asthma, and lower levels of serum IgE. A third of the patients (120 patients, 34%) exhibited low levels of serum total IgE (<1000 IU/mL). Aspergillus species were isolated from sputum in 126/213 cases (59%), and Schizophyllum commune was identified in 12 (6%) patients. During the course of the treatment, ABPA recurred in 169 (48%) cases. ConclusionsThis nationwide survey identified several unique clinical characteristics of ABPA in Japan, such as late-onset, relatively lower serum IgE levels, and frequent recurrences/flares.

The Impact of Total Immunoglobulin E Levels on Outcomes of Maximal Medical Therapy for Chronic Rhinosinusitis

Introduction:The goal of this project was to evaluate the impact of immunoglobulin E (IgE) levels on outcomes in patients with chronic rhinosinusitis (CRS) who received maximal medical therapy (MMT).Study Design:Prospective cohort study.Methods:Thirty-eight patients who underwent MMT for CRS were assigned to three different cohorts based on their IgE levels: low IgE (<25 IU), moderate (>25 to <149 IU), and high (≥150 IU). The primary outcome evaluated was MMT failure with a surgical recommendation within each IgE cohort. Secondary outcomes included changes in pre- and post-MMT scores for the Rhinosinusitis Disability Index, Chronic Sinusitis Survey, and computed tomography–based Lund-Mackay evaluation. The cohorts were substratified based on the presence of nasal polyps and nasal allergies.Results:No significant difference was found when MMT failure was compared between the cohorts in terms of quality of life. When substratified based on the presence of nasal polyps and nasal allergies, there was no significant difference between the cohorts. In the high-IgE cohort, all patients regardless of presence of nasal polyps and nasal allergic disease, frequently failed MMT and were recommended for surgery.Conclusions:Overall, IgE levels did not seem to have a significant effect on the quality of life or outcomes of MMT in the patients with CRS. However, the presence of nasal allergies regardless of IgE levels seemed to result in more frequent recommendations for surgery after MMT. In the patients with higher-IgE levels (≥150 IU), MMT seemed to fail at high rates with or without the presence of polyps or allergic disease.

The correlation of exhaled nitric oxide, atopy, and severity of allergic rhinitis in taiwanese children with moderate persistent asthma

Background: Allergic rhinitis (AR) is characterized by eosinophilic infiltration and immunoglobulin E (IgE)-mediated reaction after exposure to an allergen. Its severity may be correlated to fractional exhaled nitric oxide (FeNO). This study aimed to evaluate the correlation of FeNO and various parameters with severity of AR in Taiwanese children with moderate persistent asthma. Materials and Methods: The study enrolled 103 children aged 5–18 years with AR and moderate persistent asthma from the Outpatient Department, Mackay Memorial Hospital, Taipei. Based on Total Nasal Symptom Score (TNSS), the patients were divided into high-score group (TNSS ≥5) and low-score group (TNSS <5). Both groups were assessed and compared by FeNO, blood eosinophil percentage, serum total IgE level, specific IgE levels to 8 allergens, and pulmonary function tests. Results: The low-score group showed significantly lower FeNO (18.57 ± 14.47 vs. 26.83 ± 17.84 ppb; P < 0.05), lower blood eosinophil percentage (3.08 ± 3.43 vs. 4.53 ± 3.37%; P < 0.05), lower level of serum total IgE (232.64 ± 438.88 vs. 510.63 ± 732.64 IU/mL; P < 0.05), and lower specific IgE to Dermatophagoides pteronyssinus (Der p), Dermatophagoides farinae (Der f), and dog (1.80 ± 2.35 vs. 3.66 ± 2.23, P < 0.05; 1.78 ± 2.36 vs. 3.56 ± 2.31, P < 0.05; and 0.00 ± 0.00 vs. 0.29 ± 0.81, P < 0.05). There are no significant differences between two groups about forced expiratory volume in 1 s (FEV1) (96.95 ± 13.39 vs. 97.85 ± 14.98% predicted; P = 0.75), FEV1/forced vital capacity percentage (89.00 ± 9.78 vs. 90.20 ± 5.85%; P = 0.47), and forced expiratory flow 25%–75% (55.16 ± 18.48 vs. 56.75 ± 20.15% predicted; P = 0.68). Conclusions: Taiwanese children with moderate persistent asthma with more severe symptoms of AR are significantly associated with higher levels of FeNO, total IgE, specific IgE to Der p, Der f, and dog, and higher blood eosinophil percentage.

Utility of serum anti-cetuximab immunoglobulin E levels to identify patients at a high risk of severe hypersensitivity reaction to cetuximab.

Cetuximab is an anti-epidermal growth factor receptor antibody used for the treatment of metastatic colorectal cancer and head and neck cancer. Hypersensitivity reactions (HSRs) are associated with cetuximab use. The aim of the study was to evaluate the utility of anti-cetuximab immunoglobulin E (IgE) detection in order to identify patients at risk of HSR to cetuximab. We included patients ready to receive a first cetuximab infusion in a prospective cohort carried out at nine French centres. Pretreatment anti-cetuximab IgE levels were measured. We compared the proportion of severe HSRs in the low anti-cetuximab IgE levels (≤29 IgE arbitrary units) subgroup with that in a historical cohort of 213 patients extracted from a previous study. Of the 301 assessable patients (mean age: 60.9±9.3years, head-and-neck cancer: 77%), 66 patients (22%) had high anti-cetuximab IgE levels, and 247 patients received cetuximab (including 38 with high anti-cetuximab levels). Severe HSRs occurred in eight patients (five grade 3 and three grade 4). The proportion of severe HSRs was lower in the low anti-cetuximab IgE levels subgroup vs. the historical cohort (3/209 [1.4%] vs. 11/213 [5.2%], odds ratio, 0.27, 95% confidence interval, 0.07-0.97), and higher in high vs. low anti-cetuximab IgE levels subgroup (5/38 [13.2%] vs. 3/209 [1.4%]; odds ratio, 10.4, 95% confidence interval, 2.4-45.6). Patients with severe HSRs had higher anti-cetuximab IgE levels than patients without reaction (median, 45 vs. 2 IgE arbitrary units, P=0.006). Detection of pretreatment anti-cetuximab IgE is feasible and helpful to identify patients at risk of severe cetuximab-induced HSRs.

Normal serum IgE levels and eosinophil counts exhibited during Strongyloides stercoralis infection

Infections with parasites, such as Strongyloides stercoralis, typically cause elevated levels of serum immunoglobulin E (IgE) and eosinophils; however, co-infection with human T cell lymphotropic virus type 1 (HTLV-1) can cause lower levels of serum IgE during S. stercoralis infection. We conducted this study to determine whether serum IgE levels and eosinophil counts could also be related to other patient characteristics or symptoms. Between 1991 and 2014, we measured and compared the symptoms of 237 patients and evaluated serum IgE levels and eosinophil counts of 199 patients who were infected with S. stercoralis at the Ryukyu University Hospital and the Nishizaki Hospital. Medical records were reviewed and blood samples were taken before treatment with the anthelminthic, ivermectin, 2weeks following the first dosage, and 2weeks following the second dosage. Commonly reported symptoms included abdominal pain, diarrhea, and general fatigue. Serum IgE levels were found to be normal in patients co-infected with HTLV-1. Additionally, females and patients younger than 70years old exhibited normal serum IgE levels when infected with S. stercoralis. No factor included in our analysis was found to affect eosinophil counts. Serum IgE levels can remain within the normal range for some patients infected with S. stercoralis. Therefore, physicians should not eliminate S. stercoralis infection from the differential diagnosis solely according to findings of normal or low IgE levels.

No simple answers for the Finnish and Russian Karelia allergy contrast: Methylation of CD14 gene.

Finnish and Russian Karelian children have a highly contrasting occurrence of asthma and allergy. In these two environments, we studied associations between total serum immunoglobulin E (IgE) with methylation levels in cluster of differentiation 14 (CD14). Five hundred Finnish and Russian Karelian children were included in four groups: Finnish children with high IgE (n = 126) and low IgE (n = 124) as well as Russian children with high IgE (n = 125) and low IgE (n = 125). DNA was extracted from whole blood cells and pyrosequenced. Three CpG sites were selected in the promoter region of CD14. Methylation levels in two of the three CpG sites were higher in the Finnish compared to Russian Karelian children. In the promoter area of CD14, the Finnish compared to Russian children with low IgE had a significant (p < 0.0001) increase in methylation levels at the Amp5Site 2. Likewise, the Finnish compared to Russian children with high IgE had a significant (p = 0.003) increase in methylation levels at the Amp5Site 3. In Russian children with low vs. high IgE, there were significant differences in methylation levels, but this was not the case on the Finnish side. In the regression analysis, adding the methylation variation of CD14 to the model did not explain the higher asthma and allergy risk in the Finnish children. The methylation levels in the promoter region of CD14 gene were higher in the Finnish compared to Russian Karelian children. However, the methylation variation of this candidate gene did not explain the asthma and allergy contrast between these two areas.

A Longitudinal Study of Association between Heavy Metals and Itchy Eyes, Coughing in Chronic Cough Patients: Related with Non-Immunoglobulin E Mediated Mechanism.

The association between heavy metals exposure and respiratory diseases or allergic sensitization showing high serum immunoglobulin E (IgE) has been suggested. However, previous findings have been inconsistent and the mechanisms responsible remain unclear. We evaluated heavy metal exposure and its association with coughing, itchy eyes in chronic cough patients with different IgE levels. Ninety outpatients in Kanazawa University Hospital were recruited between January–June 2011. Subjects whose total IgE measured by radioimmunosorbent test were asked to record their daily symptoms. We collected daily total suspended particles (TSP) from which concentrations of calcium (Ca), cadmium (Cd), chromium (Cr), iron (Fe), manganese (Mn), nickel (Ni), and lead (Pb) were determined then divided into high and low level groups. Generalized estimating equations were applied to compute the relationship between concentrations of these metals and symptoms. All metals at high levels were significantly associated with itchy eyes compared with low levels, with exception of Ca, the six others were significant in patients with IgE < 250 IU/mL. Cd, Fe, Mn had association with coughing (odds ratio-OR (95% confidence interval-CI): 1.13 (1.03, 1.24), 1.22 (1.05, 1.42), and 1.13 (1.01, 1.27), respectively), this relationship remained significant for Cd (OR (95% CI): 1.14 (1.03, 1.27)) and Mn (OR (95% CI): 1.15 (1.00, 1.31)) in patients with lower IgE. Our findings demonstrate the relationship between aerial heavy metals and itchy eyes, coughing in chronic cough patients, suggesting these symptoms may be due to a non-IgE mediated mechanism.

Toll-like receptor 1 N248S polymorphism affects T helper 1 cytokine production and is associated with serum immunoglobulin E levels in Taiwanese allergic patients.

This study was carried out to investigate whether toll-like receptor-1 (TLR1) rs4833095 (N248S) variant, common in the Taiwanese population, contributes to pathogenesis of allergy. TLR2/1 ligand Pam3CSK4-stimulated cytokine production in peripheral blood mononuclear cells and monocyte-derived dendritic cells of different genotypes were measured via enzyme-linked immunosorbent assay. Ninety-three Taiwanese allergic patients (with asthma, allergic rhinitis, or atopic dermatitis) and 76 controls were recruited for genotyping. Serum immunoglobulin E (IgE) levels were evaluated in 60 allergic patients. The homozygous TLR1 C variant allele carrier had increased Pam3CSK4-induced tumor necrosis factor-α and interleukin-12 responses in peripheral blood mononuclear cells and monocyte-derived dendritic cells, respectively. Furthermore, although the C/C genotype was not associated with susceptibility to atopic diseases, it was correlated with lower total IgE levels in sera of allergic patients. Our data suggest that the TLR1 N248S polymorphism might play a role in Th1/Th2 differentiation, and the determination of serum IgE levels. However, interactions with other genetic and environmental factors might be required to contribute to risk of allergic diseases in our population.

Allergic diseases, immunoglobulin E, and autoimmune pancreatitis: a retrospective study of 22 patients

Background Autoimmune pancreatitis (AIP) is a chronic inflammatory disease of pancreas. We evaluated the clinical manifestations, imaging, and histological presentations of AIP in Chinese patients, and investigated the roles of immunoglobulin E (IgE) and allergic diseases in the diagnosis and pathogenesis of AIP. Methods The clinical records of 22 patients diagnosed with AIP were reviewed and analyzed. All patients with AIP fulfilled the 2006 revised diagnostic criteria proposed by Japan Pancreas Society or the Korean Criteria for AIP. Results Half (11/22) of AIP patients had allergic diseases. Twenty-one patients had elevated serum IgE levels, and 14 patients had IgE levels more than 3 times that of normal. There were no significant differences between the patients with higher or lower IgE, with or without allergic disease, in clinical features, laboratory tests, diffuse or focal lesions, or the choice of treatment methods; however, more complaints of body weight loss were observed in patients with higher IgE levels. Patients with higher IgE levels and with allergic diseases were more likely to have onset in March, April, May, August, September, or October. IgE levels decreased after therapy, but increased again during recurrence. Increased number of mast cells was found in the pancreatic tissue in AIP. Conclusions IgE maybe a useful marker for monitoring therapeutic response and recurrence of AIP. Allergic processes may play an important role in the pathogenesis of AIP.

Proliferative capacity and cytokine production by cells of HIV-infected and uninfected adults with different helminth infection phenotypes in South Africa.

BackgroundIt has been suggested that the proliferative capacity of cells from individuals with HIV or both HIV and helminth infections is attenuated and cytokine production is dysregulated. This study describes peripheral blood mononuclear cell proliferation capacity and cytokine profile from individuals with HIV or both HIV and helminth infections in South Africa.MethodsForty HIV-infected and 22 HIV-uninfected participants were randomly selected and stratified into different helminth infection phenotypes by egg excretion and Ascaris lumbricoides specific –immunoglobulin-E (IgE) levels. Five day cell cultures of participants, unstimulated or stimulated with Phytohaemaglutinnin, Streptokinase, HIV-1 p24 and Ascaris lumbricoides worm antigens were stained with monoclonal antibody-fluorochrome conjugates (Ki67-FITC and CTLA-APC-4). Percentage expression of Ki67 and CTLA-4 was measured to determine cell proliferation and regulation, respectively. Culture supernatants were analysed for the expression of 13 cytokines using the Bioplex (BioRad) system. Kruskal Wallis was used to test for differences in variables between helminth infected subgroups who were either having eggs in stool and high IgE (egg+IgEhi); or eggs in stool and low IgE (egg+IgElo); or no eggs in stool and high IgE (egg-IgEhi) and those without helminth infection (egg-IgElo).ResultsIndividuals excreting eggs in stool with high serum IgE (egg+IgEhi phenotype) had potent mitogen responses but consistently produced low, but statistically non-significant antigen–specific (HIV-1 p24 (p = 0.41) and Ascaris (p = 0.19) and recall antigen (Streptokinase; p = 0.31) Ki67 responses. The group also had reduced type 1 cytokines. Individuals excreting eggs in stool with low serum IgE( egg+IgElo phenotype) had a more favourable antiviral profile, characterized by higher IFNγ, IL-2, lower IL-4 and higher IL-10 production.ConclusionThe findings suggest that dual HIV/helminth infection with egg excretion and/or high Ascaris IgE phenotye may be linked with poor proliferative capacity and deleterious cytokine profile with regards to HIV control.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2334-14-499) contains supplementary material, which is available to authorized users.

IgE deficiency may indicate underlying hypogammaglobulinaemia?

Low serum immunoglobulin E (IgE) (<2 kU/L) found during allergy investigations may be a marker for other immunodeficiency states, in particular common variable immunodeficiency. The latter is characterised by recurrent...

The significance of serum total immunoglobulin E for in vitro diagnosis of allergic rhinitis

Allergic rhinitis is diagnosed by clinical parameters with no widely accepted screening test. Measurement of total serum immunoglobulin E (IgE) has limited use in the general population due to a low negative predictive value. The value of total IgE level in select populations undergoing in vitro allergy testing remains unknown. The aim of this study is to determine the utility of total serum IgE in the in vitro diagnosis of allergic rhinitis. A retrospective chart review of patients undergoing testing for allergic rhinitis was performed. Clinical parameters, total IgE level, and enzyme-linked immunosorbent assay (ELISA) for serum-specific IgE levels were analyzed with multivariate logistic regression. The positive and negative predictive values and a receiver operating characteristic (ROC) curve were used to assess the utility of total IgE in predicting serum-specific IgE test results. Records from 1073 patients were reviewed. ROC curve for total IgE >150 IU/mL (Σ 0.88) indicates good discrimination in identifying patients with sensitization by in vitro testing, whereas low total IgE level had strong negative predictive value (0.87, IgE <10) in identifying negative specific IgE testing. Multivariate logistic regression showed that differences in covariables did not significantly change the odds of a positive in vitro allergy test panel. Serum total IgE level is useful in the in vitro diagnosis of allergic rhinitis. In vitro testing for specific IgE may be unnecessary in patients with low serum total IgE, whereas high total IgE level suggests that in vitro testing would confirm specific sensitizations in patients with allergic rhinitis.

Total serum immunoglobulin E as a marker for missed antigens on in vitro allergy screening

The diagnosis of inhalant allergies involves a medical history, physical exam, and allergen sensitivity testing; allergen sensitivity can be assessed by a specific immunoglobulin E (IgE) screen for inhalant allergens. Some patients with clinical suspicion for inhalant allergies have a negative specific IgE screen, but high total IgE. We theorize that elevated total IgE may indicate a false-negative screen caused by "missed allergens" not initially identified. Study patients with a negative allergy screen and elevated IgE (>116 kU/L) were identified (n = 26). Control patients (n = 26) were defined as having a negative screen and an IgE <2.95 kU/L. Both groups were tested with an expanded specific IgE panel and completed a questionnaire about other causes of elevated IgE. The expanded panel was positive for inhalant allergens in 4 study patients (15%) and 0 control patients (p = 0.037). Within the study patients, 50% had asthma and 76.9% had chronic sinusitis. Only 2 control patients had asthma (11.5%), p = 0.003; 4 (19.2%) reported chronic sinusitis, p < 0.0001. Food allergen sensitivity was identified in 5 study patients and 1 control, p = 0.083. This pilot study evaluated patients clinically suspected of allergy with a negative inhalant IgE screen. Those with a high total IgE were more likely to have a missed inhalant allergen on expanded testing, as well as asthma and chronic sinusitis, compared to those with a low total IgE. Further investigation of "missed antigen" and the role of chronic respiratory inflammatory disease in patients with elevated total IgE is warranted.

Perivascular Mast Cells Dynamically Probe Cutaneous Blood Vessels to Capture Immunoglobulin E

Mast cells are tissue-resident immune cells that play a central role in allergic disease. These contributions are largely dependent on the acquisition of antigen-specific immunoglobulin E (IgE). Despite this requirement, studies of mast cell and IgE interactions have overlooked the mechanism by which mast cells acquire IgE from the blood. To address this gap, we developed reporter IgE molecules and employed imaging techniques to study mast cell function insitu. Our data demonstrate that skin mast cells exhibit selective uptake of IgE based on perivascular positioning. Furthermore, perivascular mast cells acquire IgE by extending cell processes across the vessel wall to capture luminal IgE. These data demonstrate how tissue mast cells acquire IgE andreveal a strategy by which extravascular cells monitor blood contents to capture molecules central to cellular function.

Erythrodermic cutaneous T-cell lymphoma: How to differentiate this rare disease from atopic dermatitis

Sézary syndrome and erythrodermic mycosis fungoides have been recognized as part of a broader spectrum of erythrodermic cutaneous T-cell lymphoma (E-CTCL). Atopic dermatitis (AD) is the most common, chronic inflammatory skin disease and can, in its most severe form, manifest as erythroderma. It is often difficult to clinically distinguish E-CTCL from various common and benign diseases presenting as erythroderma, including AD. Differentiating E-CTCL from benign inflammatory diseases is important to ensure proper disease management, and to provide accurate prognostic information. Clinical and laboratory features, including pruritus and serum levels of soluble interleukin-2 receptor, lactate dehydrogenase (LDH), immunoglobulin E (IgE), and several chemokines, do not differentiate E-CTCL from AD. In contrast, low serum allergen-specific IgE levels, presence of Sézary cells in peripheral blood, histological findings, and high CD4/CD8 ratio and CCR10 positivity in lesional skin are helpful in reaching a correct diagnosis. Patients with E-CTCL have been treated with oral etretinate, intravenous or subcutaneous interferon, bexarotene, extracorporeal photopheresis, total body surface electron beam, chemotherapy, or any combination of these modalities. Older patients, high serum LDH levels, and high number of circulating atypical lymphocytes are associated with poor prognosis.

High Levels of IgG4 Antibodies to Foods During Infancy Are Associated With Tolerance to Corresponding Foods Later in Life

Tomicić S, Norrman G, Fälth-Magnusson K, Jenmalm MC, Devenney I, Böttcher MF. Pediatr Allergy Immunol. 2009;20(1):35–41PURPOSE OF THE STUDY. To examine the serum and salivary antibody responses to food-elimination diets and to identify immunologic parameters related to oral tolerance.STUDY POPULATION. Prospective study of 89 children <2 years of age with eczema.METHODS. Children with eczema were examined at 3 time points, that is, at enrollment, after a 6-week treatment period, and at 4.5 years of age. Treatment included topical emollients and/or steroids for all children and a 6-week egg- and/or milk-elimination diet for 60 of the 89 children in the cohort of children who were diagnosed with an allergy to 1 or both foods. Laboratory data included skin-prick testing (SPT) to food allergens; total and specific serum immunoglobulin E (IgE) levels; serum IgA, IgG1, and IgG4 antibodies to ovalbumin and β-lactoglobulin; total IgA levels; and saliva IgA levels. At study completion, children were categorized as being egg or milk tolerant if the food was reintroduced into the diet after passage of a challenge in the clinic or at home.RESULTS. Of the 89 participating children, 60 were prescribed elimination diets that were based on SPT results, as follows: 24 egg, 11 milk, and 25 both. At study completion (4.5 years of age), 37 of 49 previously egg-allergic and 11 of 36 previously milk-allergic children were considered to be tolerant. Children who were egg or milk tolerant at 4.5 years of age had significantly higher levels of ovalbumin- or β-lactoglobulin–specific IgG4 at enrollment, respectively. Tolerant children also had higher food-specific IgG4/IgE ratios at 4.5 years. The highest IgG4/IgE ratios were found in children who had circulating milk- and/or egg-specific IgE antibodies but negative SPT results at enrollment. There was no significant difference between total or food-specific IgE levels at enrollment between the tolerant and nontolerant groups; however, children in the tolerant group had significantly lower food-specific IgE antibodies at 4.5 years, compared with those in the nontolerant group. There were no significant differences in total IgA, saliva IgA, or food-specific IgA levels between groups at enrollment or at 4.5 years.CONCLUSIONS. High food-specific IgG4 antibodies at <2 years of age and high IgG4/IgE ratios were related to oral tolerance to milk and egg at 4.5 years of age.REVIEWER COMMENTS. This study demonstrates that early immunologic markers may be indicators of oral tolerance acquisition among a subset of children with eczema and milk and/or egg allergy. These data may be useful in conjunction with other measures such as serum-specific IgE levels, history of past reactions, and SPT to predict future oral tolerance acquisition. One weakness of the study was the fact that participants did not undergo a diagnostic food challenge to confirm clinical reactivity at enrollment, and recommendations for food elimination were made on the basis of SPT results. It is likely that elimination diets were prescribed for some participants who were actually clinically tolerant at enrollment despite having a positive SPT result. Future studies to determine the utility of immunologic markers should confirm clinical reactivity by performing a diagnostic food challenge or confirming a convincing history of past reactions.

Common variants in FCER1A influence total serum IgE levels from cord blood up to six years of life

In a recent genome wide scan, a functional promoter variant (rs2251746) in the gene encoding the alpha chain of the high affinity receptor for immunoglobulin E (IgE) (FCER1A) was identified as major determinant of serum IgE levels. The aim of this study was to investigate the role of rs2251746 on total IgE levels measured at different stages of life from birth (cord blood) up to the age of 6 and to evaluate its interaction with the environmental influences in two German birth cohorts. Data from two German birth cohorts were analysed (n = 1043 for the LISA cohort and n = 1842 for the GINI cohort). In the studies, total serum IgE was measured from cord blood, and blood samples taken at the age of 2/3 and 6 years. In a subgroup of the LISA study, house dust samples were collected at age of 3 months and the amount of endotoxin was determined. Random effect models were used to analyse the longitudinal health outcomes. In the two cohorts, the heterozygote and the rare homozygote of rs2251746 was consistently associated with lower total IgE levels from birth up to the age of 6 years with an allele-dose effect (P < 0.02 for blood samples taken at each time point in both cohorts). No interaction between the two FCER1A encoding gene and environmental exposures including endotoxin, worm infestation and day care centre attendance during early childhood were observed. Common variants in FCER1A strongly influence basal IgE production independently from environmental stimuli. These effects can be observed already in cord blood pointing to altered gene expression in foetus.