Project description:BackgroundAllergic conjunctivitis (AC) is predominantly caused by serum specific-IgE (sIgE)-mediated type I allergy. This study aims to analyze the distribution of sIgE in children with AC, and the concomitant allergic diseases.MethodsThe clinical data from 310 children, diagnosed with AC and admitted to our hospital from January 2017 to January 2019 were retrospectively collected. The children were divided into three groups: infant group (2 months to 1 year old, 91 cases), child group (1 to 3 years old, 112 cases), and preschool group (3 to 6 years old, 107 cases). Children in every group were analyzed for positive rates, the number of positive sIgE types, the distribution of positive inhaling and ingesting allergens and concomitant allergic diseases.ResultsThe sIgE positive rate of infant was significantly lower than that of the other two groups, and the number of 18.75% sIgE positive species was 1. The number of sIgE positive species in the child group and preschool group was more than 2 (78.30%, 71.15%). The positive rate of sIgE to dust mites, house dust, animal dander, eggs, beef, mutton and mango in the preschool group was significantly higher than the other groups (P<0.05). The positive rate of sIgE to milk in infant group was significantly higher than the other two groups (P<0.05). Children in the preschool group showed the highest incidence of AC, AC + allergic rhinitis, AC + allergic rhinitis + wheezing, while those in the infant group displayed the lowest incidence (P<0.05). AC + gastrointestinal allergy, AC + atopic dermatitis, AC + gastrointestinal allergy + atopic dermatitis in infant group was significantly higher than the other two groups (P<0.05). Patients in the child group displayed a significantly higher incidence of AC + infant wheezing than the other two groups (P<0.05).ConclusionsWe correlated children's age with the positive rate and gradual increase in types of AC allergens. Concomitant allergic diseases of children with AC at different ages conform to the natural course of allergic diseases. In clinic, improving the diagnostic efficiency of AC in children, and early interventional treatment will positively contribute to their prognosis, and reduce the risk of other allergic diseases.
Project description:Allergic diseases are inflammatory disorders that involve many types of cells and factors, including allergens, immunoglobulin (Ig)E, mast cells, basophils, cytokines and soluble mediators. Among them, IgE plays a vital role in the development of acute allergic reactions and chronic inflammatory allergic diseases, making its control particularly important in the treatment of IgE-mediated allergic diseases. This review provides an overview of the current state of IgE targeted therapy development, focusing on three areas of translational research: IgE neutralization in blood; IgE-effector cell elimination; and IgE+ B cell reduction. IgE-targeted medicines such as FDA approved drug Xolair (Omalizumab) represent a promising avenue for treating IgE-mediated allergic diseases given the pernicious role of IgE in disease progression. Additionally, targeted therapy for IgE-mediated allergic diseases may be advanced through cellular treatments, including the modification of effector cells.
Project description:What is already known about this subjectOmalizumab is a humanized anti-IgE monoclonal antibody that binds and captures circulating IgE, preventing interaction with receptors on mast cells and basophils, thereby interrupting the allergic cascade. It has a well-characterized efficacy and safety profile in patients with asthma. While omalizumab is known to reduce serum free IgE concentrations, effects on total IgE and IgE production are less well characterized.What this study adds(i) Confirmation of prior hypotheses that IgE production can decrease with time when patients are given anti-IgE therapy; (ii) guidance on a biomarker, total IgE, which can be used to ascertain whether individual patients experience a change in their IgE production; and (iii) a way to assess whether patients' IgE production has been sufficiently down-regulated such that they may consider stopping anti-IgE therapy.AimTo determine whether excessive IgE production by patients with atopic allergic asthma decreases with omalizumab therapy.MethodsOmalizumab, free and total IgE data were obtained from an epidemiological study and six randomized, double-blind, placebo-controlled trials in patients with allergic asthma. The binding between omalizumab and IgE together with the production and elimination of IgE were modelled as previously, except that, in order to explain why total IgE was decreasing over a period of 5 years, the expression of IgE was allowed to change.ResultsThe prior constant IgE production model failed to converge on the data once long-term observations were included, whereas models allowing IgE production to decrease fitted. A feedback model indicated that, on average, IgE production decreased by 54% per year. This model was further developed with covariate searches indicating clinically small but statistically significant effects of age, gender, body mass index and race on some parameters. Model predictions were checked internally and externally against 3-5 year data from paediatric and adult atopic asthmatic patients and externally against extensive total IgE data from a long-duration (>1 year) phase 1 study which was not used in the model building.ConclusionsA pharmacokinetic-pharmacodynamic model incorporating omalizumab-IgE binding and feedback for control of IgE production indicates that omalizumab reduces production of IgE. This raises the possibility that indefinite treatment may not be required, only for perhaps a few years. After the initial accumulation, total IgE should provide a means to monitor IgE production and guide individual treatment decisions.
Project description:BackgroundIn addition to allergen-specific IgE (sIgE), allergen-specific IgG4 (sIgG4) antibodies are also involved in the immune response resulting from an allergen exposure. The aim of our study was to analyze sIgE and sIgG4 patterns in the most common allergic disorders: bronchial asthma, upper airway disorders and atopic dermatitis.MethodsIn this study a screening analysis of blood serum samples from 673 patients aged from 6 months to 17 years with different allergic entities was performed on microarrays. sIgE and sIgG4 levels to the most common allergens were estimated.ResultssIgE response to most pollen allergens is more strongly associated with respiratory diseases than with atopic dermatitis, while sIgE responses to cat and dog dander are more strongly associated with bronchial asthma than with atopic dermatitis and upper airway disorders such as rhinosinusitis and allergic rhinitis. A lower prevalence of sIgG4 to pollen allergens in cases of atopic dermatitis is observed compared with that in cases of asthma and upper airway disorders. Analyzing all the allergic disorders, one can see that sIgG4 response to inhalant allergens is strongly associated with sensitization to the corresponding allergen.ConclusionAllergen-specific IgE and IgG4 patterns that are relevant to concrete allergic diseases differ by sIgE and sIgG4 prevalences to defined allergens.
Project description:IntroductionChronic urticaria (CU) is not traditionally classified as an allergic disease, but emerging evidence suggests a link to atopy. The quintessential marker of atopy is IgE sensitization, there is scarce information on the IgE sensitization characteristics of CU.MethodsTo investigate IgE sensitization characteristics in CU, and compare them with classic allergic diseases. We retrospectively analyzed the results of specific IgE (sIgE) and total IgE (tIgE) in CU patients, explored the distribution patterns of these atopic markers in CU, and compared these data with those of atopic dermatitis (AD), allergic rhinitis (AR), asthma (AS), and healthy controls (HC).Results1149 patients (396 CU, 411 AD, 101 AR, 139 AS and 102 HC) were included in the study. 33.1% of CU patients showed positive sIgE and 49.0 % had elevated tIgE levels, significantly higher than those in HC. Comparative analysis with classic allergic diseases showed CU patients had a lower sIgE positivity rate but no significant difference in tIgE levels. Gender and age influenced sensitization profiles, with male CU patients showing a higher sIgE positivity rate. The distribution of sIgE levels, allergen categories, and tIgE elevated levels range in CU differed from classic allergic disease. The concordance rate between sIgE and tIgE results in CU was lower than in classic allergic disease.ConclusionOur study reveals that a significant proportion of CU patients display IgE sensitization, suggesting a clear atopic background compared to the general population. However, the IgE sensitization profile in CU differs from that of classical allergic diseases such as AD, AR, and AS, characterized by relatively lower intensity of IgE sensitization. The underlying reasons for this phenomenon and its clinical implications in CU warrant further research.
Project description:BackgroundAlthough immunoglobulin E (IgE) increases significantly in tears and serum during seasonal allergic conjunctivitis (SAC), it is unclear whether tear total IgE can reflect the severity and prognosis of SAC more accurately than serum total IgE. We aimed to investigate the usefulness of measuring the total IgE in tears to evaluate the severity and determine the treatment of SAC.MethodsThis prospective, nonrandomized study involved 55 patients with SAC and 10 age- and sex-matched healthy controls. Serum and tears were collected before and after treatment to analyze the total IgE. SAC patients received the same topical anti-allergy treatment and were followed-up every 2 weeks for 1 month. The relationship of tear and serum total IgE concentrations with pollen concentrations and symptom severity before and after treatment was assessed.ResultsThe total IgE concentration in tears was higher in SAC patients than in healthy participants with significant correlations between tear and serum total IgE concentrations. The total IgE concentration in tears, but not in serum, correlated with the pollen concentration and severity of ocular symptoms and reactions in SAC. Treatment-associated improvements in symptoms and reactions in SAC correlated with decreased concentrations of the tear total IgE. Patients with disease recurrence following treatment demonstrated significantly higher tear total IgE concentrations than patients with no recurrence.ConclusionThe total tear IgE level can indicate the severity and predict the prognosis of SAC more accurately than the serum total IgE.
Project description:PurposeThe prevalence of "ocal allergic rhinitis" within individuals suffering from perennial rhinitis remains uncertain, and patients usually are diagnosed with non-allergic rhinitis. The aim of this study was to evaluate the prevalence of a potential "local allergic rhinitis" in subjects suffering from non-allergic rhinitis in a non-selected group of young students.Methods131 students (age 25.0 ± 5.1 years) with a possible allergic rhinitis and 25 non-allergic controls without rhinitis symptoms (age 22.0 ± 2.0 years) were recruited by public postings. 97 of 131 students with rhinitis were tested positive (≥3 mm) to prick testing with 17 frequent allergens at visit 1. Twenty-four 24 subjects with a house dust mite allergy, 21 subjects with a non-allergic rhinitis, and 18 non-allergic controls were further investigated at visit 2. Blood samples were taken, and nasal secretion was examined. In addition, all groups performed a nasal provocation test with house dust mite (HDM).ResultsIn serum and nasal secretion, total IgE and house dust mite specific IgE significantly differed between HDM positive subjects and controls. However, no differences between non-allergic subjects and control subjects were quantifiable. Neither a nasal provocation test nor a nasal IgE to HDM allergens showed a measurable positive response in any of the non-allergic rhinitis subjects as well as the healthy controls, whilst being positive in 13 subjects with HDM allergy.ConclusionsNasal IgE is present in subjects with HDM allergy, but not in non-allergic rhinitis. In the investigated non-selected population, exclusive local production of IgE is absent. By implication, therefore, our findings challenge the emerging concept of local allergic rhinitis.Study identifier at ClinicalTrials.gov: NCT02810535.
Project description:BackgroundTotal IgE is a therapeutic target in patients with allergic diseases. DNA methylation in white blood cells (WBCs) was associated with total IgE levels in an epigenome-wide association study of white subjects. Whether DNA methylation of eosinophils explains these findings is insufficiently understood.MethodsWe tested for association between genome-wide DNA methylation in WBCs and total IgE levels in 2 studies of Hispanic children: the Puerto Rico Genetics of Asthma and Lifestyle Study (PR-GOAL; n = 306) and the Genes-environments and Admixture in Latino Americans (GALA II) study (n = 573). Whole-genome methylation of DNA from WBCs was measured by using the Illumina Infinium HumanMethylation450 BeadChip. Total IgE levels were measured by using the UniCAP 100 system. In PR-GOAL WBC types (ie, neutrophils, eosinophils, basophils, lymphocytes, and monocytes) in peripheral blood were measured by using Coulter Counter techniques. In the GALA II study WBC types were imputed. Multivariable linear regression was used for the analysis of DNA methylation and total IgE levels, which was first conducted separately for each cohort, and then results from the 2 cohorts were combined in a meta-analysis.ResultsCpG sites in multiple genes, including novel findings and results previously reported in white subjects, were significantly associated with total IgE levels. However, adjustment for WBC types resulted in markedly fewer significant sites. Top findings from this adjusted meta-analysis were in the genes ZFPM1 (P = 1.5 × 10-12), ACOT7 (P = 2.5 × 10-11), and MND1 (P = 1.4 × 10-9).ConclusionsIn an epigenome-wide association study adjusted for WBC types (including eosinophils), methylation changes in genes enriched in pathways relevant to asthma and immune responses were associated with total IgE levels among Hispanic children.
Project description:Abnormalities in the human microbiota are associated with the etiology of allergic diseases. Although disease site-specific microbiota may be associated with disease pathophysiology, the role of the nasal microbiota is unclear. We sought to characterize the microbiota of the site of allergic rhinitis, the inferior turbinate, in subjects with allergic rhinitis (n = 20) and healthy controls (n = 12) and to examine the relationship of mucosal microbiota with disease occurrence, sensitized allergen number, and allergen-specific and total IgE levels. Microbial dysbiosis correlated significantly with total IgE levels representing combined allergic responses but not with disease occurrence, the number of sensitized allergens, or house dust mite allergen-specific IgE levels. Compared to the populations in individuals with low total IgE levels (group IgElow), low microbial biodiversity with a high relative abundance of Firmicutes phylum (Staphylococcus aureus) and a low relative abundance of Actinobacteria phylum (Propionibacterium acnes) was observed in individuals with high total serum IgE levels (group IgEhigh). Phylogeny-based microbial functional potential predicted by the 16S rRNA gene indicated an increase in signal transduction-related genes and a decrease in energy metabolism-related genes in group IgEhigh as shown in the microbial features with atopic and/or inflammatory diseases. Thus, dysbiosis of the inferior turbinate mucosa microbiota, particularly an increase in S. aureus and a decrease in P. acnes, is linked to high total IgE levels in allergic rhinitis, suggesting that inferior turbinate microbiota may be affected by accumulated allergic responses against sensitized allergens and that site-specific microbial alterations play a potential role in disease pathophysiology.