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Background: Atopic dermatitis (AD) is caused by interactions between genetic susceptibility and environmental factors. Transmembrane protein 232 (TMEM232) is one of the genes strongly implicated in AD. Methods: In the present study, we aimed to investigate the association between AD with variants within TMEM232 based on maternal factors, including a history of allergic diseases, and sensitization to Der f. We performed a candidate gene association study involving the Cohort for Childhood Origins of Asthma and Allergic Diseases. Results: A single variant of the TMEM232 gene, rs17132261, was found to be significantly associated with AD. Subjects carrying the wild-type allele (C) of rs17132261 had higher total IgE than those carrying the variant rs17132261 (T). Multiple logistic regression analysis showed a statistically significant association between TMEM232 gene polymorphism and an increased risk of AD in one-year-old infants. Moreover, rs17132261 was associated with increased total IgE in infants with a maternal history of allergic disease. The group with the CC genotype showed a higher risk of developing AD compared to carriers of CT and TT genotypes when the mother had a history of allergic diseases or was sensitized to Der f. Conclusions: Our findings demonstrate that the TMEM232 risk allele, in combination with maternal factors, higher the total IgE, which could be a potential risk factor for AD. [ABSTRACT FROM AUTHOR]

Background: The burgeoning prevalence of food allergy-related diseases is closely associated with geographical allergen distribution and societal lifestyle paradigms. This study aims to shed light on the distribution patterns of specific IgE (sIgE) and total IgE (tIgE) reactivity to common food allergens in the Southern Chinese populace. Methods: Employing an analytical technique spanning two decades, we conducted specific IgE and total IgE on serum samples harvested from patients with food allergy-related pathologies at First Affiliated Hospital of Guangzhou Medical University from 2004 to 2023. This comprehensive examination of eight prototypical food allergens: egg white, milk, wheat, sesame, peanut, soybean, shrimp, and crab. Results: Our analysis showed a 100% positivity rate for sIgE and an 86.54% positivity rate for tIgE. Milk had the highest positive response rate, followed by egg white and shrimp. Age-stratified data indicated that milk sensitization peaked in children aged 2 years or younger, while egg white sensitization peaked between 3 and 5 years of age. Sensitization rates for the remaining six allergens increased with age. Additionally, co-sensitization was observed between milk, egg white, crab, and shrimp with other allergens. Conclusion: In common allergens of Southern China, egg white, milk, and shrimp ascend as the dominant subjects, underlining their imperative role in food allergy pathogenesis. This landscape-wide allergenic profiling, segregated across age clusters and enhanced by co-sensitization data, augments our power for early diagnosis and strategic intervention in food allergy diseases. [ABSTRACT FROM AUTHOR]

Abstract Background The burgeoning prevalence of food allergy-related diseases is closely associated with geographical allergen distribution and societal lifestyle paradigms. This study aims to shed light on the distribution patterns of specific IgE (sIgE) and total IgE (tIgE) reactivity to common food allergens in the Southern Chinese populace. Methods Employing an analytical technique spanning two decades, we conducted specific IgE and total IgE on serum samples harvested from patients with food allergy-related pathologies at First Affiliated Hospital of Guangzhou Medical University from 2004 to 2023. This comprehensive examination of eight prototypical food allergens: egg white, milk, wheat, sesame, peanut, soybean, shrimp, and crab. Results Our analysis showed a 100% positivity rate for sIgE and an 86.54% positivity rate for tIgE. Milk had the highest positive response rate, followed by egg white and shrimp. Age-stratified data indicated that milk sensitization peaked in children aged 2 years or younger, while egg white sensitization peaked between 3 and 5 years of age. Sensitization rates for the remaining six allergens increased with age. Additionally, co-sensitization was observed between milk, egg white, crab, and shrimp with other allergens. Conclusion In common allergens of Southern China, egg white, milk, and shrimp ascend as the dominant subjects, underlining their imperative role in food allergy pathogenesis. This landscape-wide allergenic profiling, segregated across age clusters and enhanced by co-sensitization data, augments our power for early diagnosis and strategic intervention in food allergy diseases.

Introduction: Two distinct chronic spontaneous urticaria (CSU) endotypes, IgE-mediated autoallergic and IgG-mediated autoimmune, were defined based on the response patterns to omalizumab. However, the coexistence of IgE and IgG autoantibodies in a subset of patients might complicate the prediction of the treatment outcomes. This study aimed to evaluate the effectiveness and safety of omalizumab in CSU patients, focusing on the factors predicting the response patterns. Methods: This was a retrospective cross-sectional single-center study investigating CSU patients treated with omalizumab for at least 6 months between September 2015 and February 2023. Patients were evaluated regarding demographics, clinical findings, baseline laboratory parameters, treatment outcomes, and side effects. Early and late responders were defined depending on the time for response, within or after 3 months, respectively. Results: Among 82 patients, 75 (91.5%) responded to omalizumab during the first 6 months, classified as early (n = 51) and late responders (n = 24). The IgG anti-thyroid peroxidase (anti-TPO)/total IgE ratio was an independent predictor for determining the speed of response (p < 0.05). Of 29 patients who discontinued omalizumab, 19 (65.5%) experienced relapse with a good response to retreatment (n = 18/19, 94.7%). Early responders relapsed more frequently than late responders (77.3% vs. 28.6%) (p < 0.05). Only mild side effects were observed in a minority of patients (n = 8/82, 9.8%). Conclusion: Omalizumab is an effective and safe treatment in CSU. The IgG anti-TPO/total IgE ratio seems a valuable tool to predict the early and late responders, the former having a higher possibility of relapse upon drug withdrawal. [ABSTRACT FROM AUTHOR]

Background: Seafood allergy (SA), including allergy to shellfish (crustacean and mollusks) and fish, is among the 4 most common food allergies causing anaphylaxis, but there are limited data showing SA clinical management in different countries. Objective: We sought to characterize a large cohort of patients with fish and shellfish allergy and to facilitate standardization of future care for this increasingly common allergic disease. Methods: We performed a retrospective, observational, noninterventional study from 945 patients from 2015 to 2019 in 7 hospitals in the United States and the United Kingdom to evaluate SA. A chi-square test was used to detect differences in family history, medical history, and current symptoms between patients in 2 countries. Results: Underdiagnosed anaphylaxis in patients with SA was associated with underuse of epinephrine (adrenaline) autoinjectors in both countries. Oral food challenge was used only when skin or serologic test results were negative. Asthma and allergic rhinitis were more common in the US patients with SA, but eczema was more common in UK patients with SA (P < .001). Respiratory, gastrointestinal, and neurological symptoms were higher in UK patients with SA than in US patients with SA (P < .001). Conclusions: In international multicenter cohorts of patients with fish and shellfish allergy, there are opportunities for improvement in management. Physician identification of anaphylaxis, use of diagnostic oral food challenges, and anaphylaxis treatment with epinephrine are areas with significant knowledge gaps in need of improvement in the United Kingdom and the United States. There is an opportunity for the development of unified, standardized diagnostic protocols for SA with distribution for allergists and trainees.

Abstract Background Recent studies have found that total immunoglobulin E (IgE) and allergen-specific IgE were associated with some metabolic diseases. However, the role of IgE in metabolism among adolescents is still unclear. Herein, this study aims to investigate the associations of serum total IgE and allergen-specific IgE with insulin resistance (IR) in adolescents, in order to provide some reference for the prevention and treatment of metabolic diseases in a young age. Methods Data of 870 adolescents were extracted from the National Health and Nutrition Examination Survey (NHANES) database in 2005–2006 in this cross-sectional study. Weighted univariate and multivariate logistic regression analyses were utilized to screen covariates and explore the relationships of serum total IgE and allergen-specific IgE with IR. The evaluation indexes were odds ratios (ORs) and 95% confidence intervals (CIs). In addition, these relationships were also assessed in subgroups of allergy history, asthma history, and number of allergens. Results Among eligible adolescents, 168 had IR. No significant association between serum total IgE level and IR was found. However, adolescents with higher level of allergen-specific IgE to rye grass [OR = 0.47, 95%CI: (0.25–0.91)], white oak [OR = 0.57, 95%CI: (0.37–0.88)], or peanut [OR = 0.38, 95%CI: (0.15–0.97)] seemed to have lower odds of IR, whereas those had higher level of shrimp-specific IgE [OR = 2.65, 95%CI: (1.21–5.84)] have increased odds of IR. In addition, these associations between allergen-specific IgE and IR were also discovered in adolescents who had allergy history or asthma history, or had different numbers of allergens. Conclusion Paying attention to different allergens in adolescents may be important in the early identification of IR among this high-risk population. The study results relatively provided some reference for further exploration on IR prevention.

Background: Recent studies have found that total immunoglobulin E (IgE) and allergen-specific IgE were associated with some metabolic diseases. However, the role of IgE in metabolism among adolescents is still unclear. Herein, this study aims to investigate the associations of serum total IgE and allergen-specific IgE with insulin resistance (IR) in adolescents, in order to provide some reference for the prevention and treatment of metabolic diseases in a young age. Methods: Data of 870 adolescents were extracted from the National Health and Nutrition Examination Survey (NHANES) database in 2005–2006 in this cross-sectional study. Weighted univariate and multivariate logistic regression analyses were utilized to screen covariates and explore the relationships of serum total IgE and allergen-specific IgE with IR. The evaluation indexes were odds ratios (ORs) and 95% confidence intervals (CIs). In addition, these relationships were also assessed in subgroups of allergy history, asthma history, and number of allergens. Results: Among eligible adolescents, 168 had IR. No significant association between serum total IgE level and IR was found. However, adolescents with higher level of allergen-specific IgE to rye grass [OR = 0.47, 95%CI: (0.25–0.91)], white oak [OR = 0.57, 95%CI: (0.37–0.88)], or peanut [OR = 0.38, 95%CI: (0.15–0.97)] seemed to have lower odds of IR, whereas those had higher level of shrimp-specific IgE [OR = 2.65, 95%CI: (1.21–5.84)] have increased odds of IR. In addition, these associations between allergen-specific IgE and IR were also discovered in adolescents who had allergy history or asthma history, or had different numbers of allergens. Conclusion: Paying attention to different allergens in adolescents may be important in the early identification of IR among this high-risk population. The study results relatively provided some reference for further exploration on IR prevention. [ABSTRACT FROM AUTHOR]

Most genetic studies of asthma and allergy have focused on common variation in individuals primarily of European ancestry. Studying the role of rare variation in quantitative phenotypes and in asthma phenotypes in populations of diverse ancestries can provide additional, important insights into the development of these traits. We sought to examine the contribution of rare variants to different asthma- or allergy-associated quantitative traits in children with diverse ancestries and explore their role in asthma phenotypes. We examined whole-genome sequencing data from children participants in longitudinal studies of asthma (n = 1035; parent-identified as 67% Black and 25% Hispanic) to identify rare variants (minor allele frequency < 0.01). We assigned variants to genes and tested for associations using an omnibus variant-set test between each of 24,902 genes and 8 asthma-associated quantitative traits. On combining our results with external data on predicted gene expression in humans and mouse knockout studies, we identified 3 candidate genes. A burden of rare variants in each gene and in a combined 3-gene score was tested for its associations with clinical phenotypes of asthma. Finally, published single-cell gene expression data in lower airway mucosal cells after allergen challenge were used to assess transcriptional responses to allergen. Rare variants in USF1 were significantly associated with blood neutrophil count (P = 2.18 × 10−7); rare variants in TNFRSF21 with total IgE (P = 6.47 × 10−6) and PIK3R6 with eosinophil count (P = 4.10 × 10−5) reached suggestive significance. These 3 findings were supported by independent data from human and mouse studies. A burden of rare variants in TNFRSF21 and in a 3-gene score was associated with allergy-related phenotypes in cohorts of children with mild and severe asthma. Furthermore, TNFRSF21 was significantly upregulated in bronchial basal epithelial cells from adults with allergic asthma but not in adults with allergies (but not asthma) after allergen challenge. We report novel associations between rare variants in genes and allergic and inflammatory phenotypes in children with diverse ancestries, highlighting TNFRSF21 as contributing to the development of allergic asthma. [ABSTRACT FROM AUTHOR]

In vitro specific IgE (sIgE) testing has become an important tool for the diagnosis of IgE-mediated allergic diseases. Current methods used to detect allergen sIgE are time consuming and/or expensive. Therefore, a new method was developed for rapid quantitative detection of cat dander-sIgE antibody based on homogeneous chemiluminescence immunoassay. Selection of chemibeads with different chemical groups, and the best Light-initiated chemiluminescence assay (LiCA) analytical mode for cat dander-sIgE detection. To validate and eliminate the interference of IgE on the detection of cat dander-sIgE, concentration of biotinylated anti-human IgE antibody was optimized. For quantification of cat dander-sIgE, a calibration curve was established, and the performance of the assay was evaluated according to clinical guidelines. Indirect LiCA is the best mode of analysis and biotinylated anti-human IgE antibody at a dilution ratio of 1:250 minimizes IgE interference. The coefficient of variation of the developed LiCA was 1.49% to 4.66%, with an intermediate precision of 6.90% to 8.21%. The LoB, LoD, and LoQ of the assay were 0.023 kUA/L, 0.056 kUA/L and 0.185 kUA/L. The coefficient of correlation (r) between LiCA and ImmounoCAP was 0.9478. A cat dander-sIgE quantitation assay based on homogeneous chemiluminescence immunoassay was established, which could be a new reliable analytical tool for the determination of cat dander-sIgE. [ABSTRACT FROM AUTHOR]

Little is known about nasal epithelial gene expression and total IgE in youth. We aimed to identify genes whose nasal epithelial expression differs by total IgE in youth, and group them into modules that could be mapped to airway epithelial cell types. We conducted a transcriptome-wide association study of total IgE in 469 Puerto Ricans aged 9 to 20 years who participated in the Epigenetic Variation and Childhood Asthma in Puerto Ricans study, separately in all subjects and in those with asthma. We then attempted to replicate top findings for each analysis using data from 3 cohorts. Genes with a Benjamini-Hochberg–adjusted P value of less than.05 in the Epigenetic Variation and Childhood Asthma in Puerto Ricans study and a P value of less than.05 in the same direction of association in 1 or more replication cohort were considered differentially expressed genes (DEGs). DEGs for total IgE in subjects with asthma were further dissected into gene modules using coexpression analysis, and such modules were mapped to specific cell types in airway epithelia using public single-cell RNA-sequencing data. A higher number of DEGs for total IgE were identified in subjects with asthma (n = 1179 DEGs) than in all subjects (n = 631 DEGs). In subjects with asthma, DEGs were mapped to 11 gene modules. The top module for positive correlation with total IgE was mapped to myoepithelial and mucus secretory cells in lower airway epithelia and was regulated by IL-4, IL5, IL-13, and IL-33. Within this module, hub genes included CDH26 , FETUB , NTRK2 , CCBL1 , CST1 , and CST2. Furthermore, an enrichment analysis showed overrepresentation of genes in signaling pathways for synaptogenesis, IL-13, and ferroptosis, supporting interactions between interleukin- and acetylcholine-induced responses. Our findings for nasal epithelial gene expression support neuroimmune coregulation of total IgE in youth with asthma. [ABSTRACT FROM AUTHOR]

Background: Treating chronic urticaria (CU) that is unresponsive to H1-antihistamines (H1AHs) is challenging, and the real-world effectiveness of omalizumab remains unclear. Objective: Our aim was to evaluate the real-world effectiveness of omalizumab, optimal response assessment timing, and predictive factors. Methods: Initially, 5535 patients with CU who were receiving at least 20 mg of loratadine daily for at least 6 months (January 2007-August 2021) were screened. Ultimately, 386 patients who had been receiving omalizumab add-on treatment for >6 months were followed-up for more than 2 years. Predictors of treatment response to omalizumab add-on therapy for patients with antihistamine-refractory CU were identified by using a generalized linear model. Results: In our retrospective cohort, omalizumab treatment showed cumulative response rates of 55.2% at 3 months, 71.0% at 6 months, and 81.4% at 9 months for patients with H1AH-refractory CU. Analysis of longitudinal responses to omalizumab treatment revealed 3 distinct clusters: favorable (cluster 1 [n = 158]), intermediate (cluster 2 [n =1 43]), and poor responses (cluster 3 [n = 85]). Subjects were categorized on the basis of whether they had achieved a complete response within 3 months; 213 early responders, 117 late responders, and 56 nonresponders were identified. The initial dose of omalizumab differed significantly among the 3 clusters. Low total IgE level (

Background: Total immunoglobulin E (IgE) analysis is a common tool in allergy diagnosis. Suggested reference values for IgE are divergent and sometimes based on outdated assay methods. We aimed to validate the published reference values (geometric mean [GM]: 13.2 kU/L, upper limit of normal [ULN], 114 kU/L) shown in an Uppsala cohort from 1974 using Phadebas IgE PRIST, and the suggested clinical threshold of 100 kU/L (Zetterström and Johansson 1981). Methods: Immunoglobulin E was measured in two Uppsala cohorts from 1997 (Blood bank) and 2011 to 2013 (the European community respiratory health survey part III [ECRHS III]) using ImmunoCAP™ Total IgE. For the reference value calculations, exclusion criteria were atopy (both cohorts), doctor’s diagnosis of asthma and self-reported allergy (hay fever, rhinitis, rash) (only ECRHS III). Upper limit of normal was defined as mean + 2 standard deviations (SD) calculated using log-transformed values and back-transformation of the ULN prior to presentation. Common imputation methods for results below the assay range were evaluated. Results: The average GM was 14.2 kU/L (Blood bank, n = 63; imputation method range: 16.9–17.4 kU/L; ECRHS III, n = 113: 10.7–11.6 kU/L) and the overall mean ULN was 118 kU/L (Blood bank: 113–130 kU/L; ECRHS III: 104–128 kU/L). The clinical sensitivity and specificity of the 100 kU/L IgE threshold were 37.8 and 94.3% for atopy, 34.9 and 89.5% for doctor’s diagnosis of asthma, and 24.5 and 97.3% for any self-reported allergy (ECRHS III). Conclusion: The calculated ULN values were similar between the cohorts. We conclude that the total IgE reference values shown for Uppsala subjects from 1974 are still valid and suitable also for the ImmunoCAP Total IgE assay. The 100 kU/L threshold for total IgE had a low sensitivity but high specificity for atopy, asthma, and allergy.

House dust mite (HDM)-allergic asthma is an abnormal immune response to extrinsic aeroallergens found in human vicinities. Studying the role of the associated immunity biomarkers and their interplay helps in discovering novel therapeutic strategies that can be used in adjunct with effective long-term immunotherapy. This study investigates the total serum IgE, FoxO1, and Sirtuin 1 (SIRT1) gene expressions in HDM-allergic asthma patients. We enrolled 40 patients for each of the following three groups: an HV group of healthy volunteers and HDM/AA and HDM/SCIT groups of HDM-allergic asthma patients who did not and who did receive immunotherapy before recruitment in this study, respectively. The results elucidated that total IgE was strikingly elevated in the HDM/AA group and showed little decline in the HDM/SCIT group. Both FoxO1 and SIRT1 gene expressions showed the highest levels in the HDM/SCIT group. There was a negative correlation between total IgE and both FoxO1 and SIRT1 in the HDM/AA group while there was a positive correlation with SIRT1 in the HDM/SCIT group. In conclusion, the interplay of the three immunity biomarkers related to HDM-allergic asthma after the course of immunotherapy treatment suggests further, broader studies on the feasibility of their role as immunity biomarkers in the control and remission of HDM-allergic asthma.

BackgroundAsthma is a heterogeneous disease. Clinical blood parameters differ by race/ethnicity and are used to distinguish asthma subtypes and inform therapies. Differences in subtypes may explain population-specific trends in asthma outcomes. However, these differences in racial/ethnic minority pediatric populations are unclear.ObjectiveWe investigated the association of blood parameters and asthma subtypes with asthma outcomes and examined population-specific eligibility for biologic therapies in minority pediatric populations.MethodsUsing data from 2 asthma case-control studies of pediatric minority populations, we performed case-control (N = 3738) and case-only (N = 2743) logistic regressions to quantify the association of blood parameters and asthma subtypes with asthma outcomes. Heterogeneity of these associations was tested using an interaction term between race/ethnicity and each exposure. Differences in therapeutic eligibility were investigated using chi-square tests.ResultsRace/ethnicity modified the association between total IgE and asthma exacerbations. Elevated IgE level was associated with worse asthma outcomes in Puerto Ricans. Allergic asthma was associated with worse outcomes in Mexican Americans, whereas eosinophilic asthma was associated with worse outcomes in Puerto Ricans. A lower proportion of Puerto Ricans met dosing criteria for allergic asthma-directed biologic therapy than other groups. A higher proportion of Puerto Ricans qualified for eosinophilic asthma-directed biologic therapy than African Americans.ConclusionsWe found population-specific associations between blood parameters and asthma subtypes with asthma outcomes. Our findings suggest that eligibility for asthma biologic therapies differs across pediatric racial/ethnic populations. These findings call for more studies in diverse populations for equitable treatment of minority patients with asthma.

Abstract Background Our study aimed to investigate whether serum total IgE and blood eosinophils were associated with radiological features of bronchiectasis in a Chinese cohort. Methods We retrospectively enrolled bronchiectasis patients who visited Peking University Third Hospital from Jan 1st, 2012 to Oct 7th, 2021. The clinical, laboratory and chest CT characteristics were analyzed in association with serum total IgE level and blood eosinophil count. Results A total of 125 bronchiectasis patients were enrolled, with 50.4% (63/125) female, and a mean age of 62.4 ± 14.1 years. The median serum total IgE level and blood eosinophil count were 47.7 (19.8, 123.0) KU/L and 140 (90, 230) cells/µl, respectively. In patients with a higher than normal (normal range, 0–60 KU/L) total IgE (43.2%, n = 54), more lobes were involved [4 (3, 5) vs. 3 (2, 4), p = 0.008], and mucus plugs were more common (25.9% vs. 9.9%, p =0.017) on HRCT, as compared to those with a normal level of total IgE. The higher IgE group was more likely to have bilateral involvement (p = 0.059), and had numerically higher Smith and Bhalla scores, but the differences were not statistically significant. In patients with an eosinophil count ≥ 150 cells/µl (49.6%, n = 62), the number of lobes involved was greater [4 (3, 5) vs. 3 (2, 4), p = 0.015], and the Smith and Bhalla scores were higher [9 (5, 12) vs. 6 (3, 9), p = 0.009, 7 (5, 11) vs. 5 (3, 9), p = 0.036]. The Smith score was correlated positively with the eosinophil count (r = 0.207, p = 0.020). Fractional exhaled nitric oxide (FeNO) was correlated with total IgE (r = 0.404, p = 0.001) and eosinophil count (r = 0.310, p = 0.014). Conclusions Our study demonstrated that serum total IgE and the blood eosinophil count were associated with the radiological extent and severity of bronchiectasis, necessitating further investigation on the role of T2 inflammation in structural abnormalities of this heterogeneous disease.

Abstract Objective The study was to investigate serum total IgE levels and the distribution of specific IgE types in children aged 6–9 years with tic disorder, in order to provide knowledge for diagnosis and treatment of children with tic disorder. Methods Total serum IgE levels were detected by enzyme-linked immunosorbent assay (ELISA). Specific IgE levels in 72 children with tic disorder and normal 31 children were detected by EUROblot, respectively. Results The total serum IgE level of children with tic disorder aged 6–9 years was significantly higher than those of children in control group. Specific IgE distribution in tic disorder group was observed increased mainly including inhaled mugwort, dust mite combination 1 (house dust mite/dust mite), mold combination (penicillium point/mycobacteria/Aspergillus fumigatus/streptomyces), cockroaches in Germany respectively, and also food freshwater fish combination 1 (salmon/sea bass/carp), marine fish combination 1 (cod/lobster/scallop), egg white, and crab, while elevated specific IgE of normal children group was mainly food-based (egg white, milk, and soybean). The significant different specific IgE between two groups was dust mite combination 1 (house dust mite/dust mite) (P

Objective: Allergic diseases, infections, parasitic infections, hematologic malignancies, chronic lung diseases, inflammatory diseases, cystic fibrosis, nephrotic syndrome and primary immunodeficiencies (PIDs) are the main disorders in the differential diagnosis of elevated serum IgE levels. The aim of this study was to evaluate the differential clinical diagnosis of patients whose serum IgE levels were found to be above 2000 IU/ml when measured at the pediatric allergy and immunology outpatient clinics of our hospital. Materials and Methods: This was a retrospective study of children aged between 2 months to 18 years referred to the Pediatric Allergy and Immunology clinics and evaluated at our hospital between October 2010 and March 2021. Results: In the 480 patients with serum total IgE levels exceeding 2000 IU/ml in this study, allergic diseases were observed in 313 (65.2%) patients, primary immunodeficiencies in 28 (5.8%), infectious diseases in 12 (2.4%), hematological diseases in 14 (2.8%), rheumatologic diseases in 5 (1%), and other diseases in 2 (0.4%), while 113 (23.5%) patients were undefined. Conclusion: This study revealed that allergic diseases were the most common cause of extremely elevated serum IgE levels, while 5.8% of the patients were diagnosed with primary immunodeficiencies. Our study indicates that primary immunodeficiencies, although rare, should be kept in mind in patients with a serum total IgE above 2000 IU/ml. [ABSTRACT FROM AUTHOR]

Purposeof Review: Chronic spontaneous urticaria and chronic inducible urticaria (CSU/CindU) are caused by mast cell and basophil activation leading to degranulation and the release of histamine and several other mediators. Three kinds of factors can trigger mast cells in CSU: (1) activation of stimulating receptor(s) on the mast cell membrane, (2) upregulation of certain receptor(s), and (3) intracellular dysregulation in signaling with overexpression of the spleen tyrosine kinase (SYK) or reduced activation of the inhibitory Src homology 2 (SH2)-containing inositol phosphatases (SHIP)-related pathways. In CSU, two major endotypes exist based on the primary receptor activating mechanism: type I hypersensitivity (IgE-mediated, directed against auto-allergens) and type IIb (autoimmune, via IgG autoantibodies directed against IgE or the IgE-receptor). Their treatment responses vary. We discuss in vitro and in vivo biomarkers. Recent Findings: Patients with auto-allergic CSU have clinical characteristics that can distinguish them partly from those with autoimmune CSU. Most importantly, their disease generally presents a less aggressive course, a better response to second generation (up-dosed) antihistamines and a good response to omalizumab, if necessary. Meanwhile, autoimmune CSU/CindU patients fare less well and often need immunosuppressive drugs. Biomarkers that might help endotype CSU/CindU patients and select the most appropriate treatment, dose, and duration, e.g., for autoallergic CSU, high total IgE and IgE against auto-allergens; for autoimmune CSU, low IgE, basopenia, and IgG against autoantigens like thyroid peroxidase and a positive autologous serum skin test (but sometimes also positive in autoallergy). Summary: Some biomarkers are easily accessible but of low specificity; others are highly specific but more futuristic. [ABSTRACT FROM AUTHOR]

Background: Fraction of exhaled nitric oxide (FeNO) is used for diagnosing and monitoring asthma in children, but the influence of allergic sensitization is still poorly understood. Here, we investigate how asthma and allergic sensitization influence FeNO levels during childhood. Methods: We investigated the associations between asthma, aeroallergen sensitization, and FeNO measured from age 5–18 years in the COPSAC2000 birth cohort of 411 children using repeated measurement mixed models adjusted for gestational age, sex, concurrent airway infection, inhaled corticosteroids, and tobacco exposure. Replication was sought in the similarly designed COPSAC2010 cohort of 700 children. Results: In the COPSAC2000 cohort, 133 had asthma between age 5 and 18 years, and in the COPSAC2010 cohort, 112 had asthma between age 5 and 10 years. In the COPSAC2000 cohort, asthma and aeroallergen sensitization were both associated with higher FeNO from age 5 to 18 years: adjusted geometric mean ratio (aGMR), 1.22 (1.08–1.35), p <.01, and 1.41 (1.21–1.65), p < 0.001, respectively. However, asthma was associated with increased FeNO among children with aeroallergen sensitization: 1.44 (1.23–1.69), p <.0001, whereas asthma was associated with decreased FeNO among nonsensitized children: 0.80 (0.65–0.99), p =.05 (p‐interaction<.0001 for asthma x sensitization). Replication in the COPSAC2010 cohort showed similar results (p‐interaction <.01). Further, blood eosinophil count, total‐IgE, bronchodilator response, and bronchial hyperreactivity were all associated with increased FeNO among children sensitized to aeroallergens, but not among nonsensitized children. Conclusion: Fraction of exhaled nitric oxide is elevated through childhood in children with asthma and is correlated with asthma‐associated traits depending on the presence of aeroallergen sensitization. These findings indicate that FeNO is only a valid asthma biomarker in children with concurrent aeroallergen sensitization, which is important for guideline recommendations on the clinical use of FeNO. [ABSTRACT FROM AUTHOR]

Objectives: There appears to be marked discrepancies between total IgE reference intervals (RIs) in use by many laboratories and those recommended by published studies. The aim of this study was therefore to review total IgE RIs currently reported by Scandinavian and British laboratories and to compare these to published RIs identified by a literature review. Methods: Relevant laboratories were identified by test directories provided by the national accreditation bodies in Norway, Sweden, Denmark and the UK. Total IgE RIs and their sources were acquired by accessing laboratory user handbooks or by an electronic survey. In addition a literature review of published total IgE RI studies was performed. Results: From 172 accredited laboratories providing total IgE analysis, data was acquired from 122 laboratories. An adult upper reference limit between 81 to 150 kU/L was reported by 89% of these. Denmark and Sweden reported the most harmonised RIs whilst Norway and the UK exhibited the least degree of harmonisation. Published adult (n = 6) and paediatric (n = 6) RI studies reported markedly higher upper limits than those currently in use by the laboratories included in this study. There were also large variations in the number of age strata in use for paediatric RIs. Conclusion: This study demonstrates large variations in currently utilised IgE RIs by Scandinavian and British accredited laboratories and most report markedly lower RIs than those recommended by recent RI publications. Many laboratories likely utilise outdated RIs and should consider critically reviewing and updating their RIs. [ABSTRACT FROM AUTHOR]

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Purpose: Despite their effects on human health, the link between smokeless tobacco (ST) consumption and asthma severity in asthmatic patients is still unknown. Thus, the present study aims to complete the lack of information by investigating the aggravation of inflammation, aggravation of asthma, oxidative stress and cytotoxicity induced by ST in asthmatic patients. Methods: The study recruited 80 male volunteers residing in Annaba town, Algeria, divided into four groups by using a questionnaire, each group consisting of 20 male volunteers. Herein, biochemical parameters, hematological parameters, C-reactive protein (CRP), total IgE, interleukin-5 (IL-5), nitric oxide and oxidative stress were measured. Results: The obtained results showed that ST clearly enhanced lung inflammation and aggravation of asthma through total IgE, IL-5 and CRP increased production. In addition, ST was found to intensify oxidative stress via increased lipid peroxidation and decreased reduced glutathione (GSH) levels. Likewise, the biochemical and hematological parameters results showed that ST causes damage and inflammation to tissues. Conclusion: Therefore, our study reveals that ST obviously enhances allergic inflammation in patients suffering from asthma. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Atopic diseases are the most common chronic conditions in childhood. The best treatment for allergic disease is possible with early diagnosis. The purpose of the study was to assess the predictive value of total immunoglobulin E (IgE) and eosinophil levels for allergy test positivity in patients diagnosed with asthma, allergic rhinitis (AR), atopic dermatitis (AD), and food allergy (FA). METHODS: Pediatric patients between 0 and 18 years old diagnosed with asthma, AR, AD, and FA were included in the study. Demographic characteristics of the patients, total IgE, eosinophil (absolute and %) values, specific igE (SPIGE), and skin prick test (SPT) results were recorded. RESULTS: The data of 2665 patients were evaluated in the study. Of the patients, 58.6% were male, whereas 41.4% were female. The median age of the children was significantly higher both in SPT-positive and SPIGE-positive patients (p<0.001). If the criteria positivity is accepted as total IgE value is =104.5 (for AD: 86.5, asthma: 116.5, AR: 120.5, FA: 42.5) and absolute eosinophil =500 and/or eosinophil (%) =5%; test positivity was higher for each disease and all patients (p<0.001). CONCLUSION: Total IgE and eosinophil levels can be used to identify atopy in patients with symptoms of AD, asthma, and AR. Total IgE and eosinophil values are suitable and easily obtainable parameters for better evaluation of health-care resources for the diagnosis and follow-up of atopic illnesses. [ABSTRACT FROM AUTHOR]

Objective: The study was to investigate serum total IgE levels and the distribution of specific IgE types in children aged 6–9 years with tic disorder, in order to provide knowledge for diagnosis and treatment of children with tic disorder. Methods: Total serum IgE levels were detected by enzyme-linked immunosorbent assay (ELISA). Specific IgE levels in 72 children with tic disorder and normal 31 children were detected by EUROblot, respectively. Results: The total serum IgE level of children with tic disorder aged 6–9 years was significantly higher than those of children in control group. Specific IgE distribution in tic disorder group was observed increased mainly including inhaled mugwort, dust mite combination 1 (house dust mite/dust mite), mold combination (penicillium point/mycobacteria/Aspergillus fumigatus/streptomyces), cockroaches in Germany respectively, and also food freshwater fish combination 1 (salmon/sea bass/carp), marine fish combination 1 (cod/lobster/scallop), egg white, and crab, while elevated specific IgE of normal children group was mainly food-based (egg white, milk, and soybean). The significant different specific IgE between two groups was dust mite combination 1 (house dust mite/dust mite) (P < 0.05). Conclusion: The total serum IgE level of children with tic disorder aged 6–9 years was significantly increased, which may be related to the disease. Specific IgE in children with tic disorder was mainly inhalation allergens, especially dust mite combination 1 (house dust mite/dust mite), which should be avoided in clinical diagnosis and daily life. [ABSTRACT FROM AUTHOR]

Background: Our study aimed to investigate whether serum total IgE and blood eosinophils were associated with radiological features of bronchiectasis in a Chinese cohort. Methods: We retrospectively enrolled bronchiectasis patients who visited Peking University Third Hospital from Jan 1st, 2012 to Oct 7th, 2021. The clinical, laboratory and chest CT characteristics were analyzed in association with serum total IgE level and blood eosinophil count. Results: A total of 125 bronchiectasis patients were enrolled, with 50.4% (63/125) female, and a mean age of 62.4 ± 14.1 years. The median serum total IgE level and blood eosinophil count were 47.7 (19.8, 123.0) KU/L and 140 (90, 230) cells/µl, respectively. In patients with a higher than normal (normal range, 0–60 KU/L) total IgE (43.2%, n = 54), more lobes were involved [4 (3, 5) vs. 3 (2, 4), p = 0.008], and mucus plugs were more common (25.9% vs. 9.9%, p =0.017) on HRCT, as compared to those with a normal level of total IgE. The higher IgE group was more likely to have bilateral involvement (p = 0.059), and had numerically higher Smith and Bhalla scores, but the differences were not statistically significant. In patients with an eosinophil count ≥ 150 cells/µl (49.6%, n = 62), the number of lobes involved was greater [4 (3, 5) vs. 3 (2, 4), p = 0.015], and the Smith and Bhalla scores were higher [9 (5, 12) vs. 6 (3, 9), p = 0.009, 7 (5, 11) vs. 5 (3, 9), p = 0.036]. The Smith score was correlated positively with the eosinophil count (r = 0.207, p = 0.020). Fractional exhaled nitric oxide (FeNO) was correlated with total IgE (r = 0.404, p = 0.001) and eosinophil count (r = 0.310, p = 0.014). Conclusions: Our study demonstrated that serum total IgE and the blood eosinophil count were associated with the radiological extent and severity of bronchiectasis, necessitating further investigation on the role of T2 inflammation in structural abnormalities of this heterogeneous disease. [ABSTRACT FROM AUTHOR]

Case 1: A 51 year old female K/C/O Bronchial asthma with allergic rhinosinusites on inhale corticosteroids and bronchodilators since 1998 was on oral steroids and antihistamines during acute exacerbations. She was diagnosed as PTB on radiological bases in 2006 and was put on ATT for 16 months and declared cured. later on in 2011 she was again started on ATT as a case of relapse CT showing mediastinal adenopathy with parenchymal infiltrates. She presented to us in 2012, thorough investigations were performed total IgE and IgE to Aspergillus Fumigatus were elevated which wassuggestive of ABPA. Case 2: A 30 yr old non-smoker hood. H/o recurrent LRTI since 3 years and was treated with various antibiotics, Hetrazan, oral/inhaled corticosteroids and bronchodilators. He presented to us with symptoms of Exacerbation investigated Total IgE and IgE to Aspergillus Fumigatus were markedly elevated which s/o ABPA. Case 3: A 21 yr old male H/o Breathlessness since childhood. Pt was admitted in GMC Belagaviand was diagnosed with R abscess and treated with IV antibiotics for a period of 10 days and was discharged on oral antibiotics for 20 days .Pt presented to us after 1 month of discharge from GMC with C/o Cough with foul smelling expectoration fever, Nausea, vomiting and reduced appetite .After thorough investigation which showed increase in Total IgE and IgE to Aspergillus Fumigatus which s/o ABPA [ABSTRACT FROM AUTHOR]

Background: Together with impaired mucociliary clearance, lung disease in cystic fibrosis (CF) is driven by dysregulation of innate and adaptive immunity caused by dysfunctional CFTR (Cystic Fibrosis Transmembrane Conductance Regulator), leading to airway infection and hyperinflamma-tion. The highly effective CFTR modulator therapy (HEMT) elexacaftor/tezacaftor/ivacaftor (ETI) generates substantial improvements in clinical outcomes of people with CF (pwCF) by restoration of CFTR activity. Aberrant immune responses of lymphocytes due to CFTR dysfunction has been described in the past, but not the effects of CFTR restoration by HEMT on these cells. We aimed to examine the effect of ETI on the proliferative activity of antigen-specific CD154 (+) T cells against bacterial and fungal species relevant inCF and on total IgGand IgE asmarkers of B cell adaptive immunity. Methods: We performed ex vivo analyses of Ki-67 expression in antigen-specific CD154 (+) T cells against Pseudomonas aeruginosa, Staphylococcus aureus, Aspergillus fumigatus, Scedosporium apiospermum and Candida albicans from 21 pwCF by cytometric assay based on antigen-reactive T cell enrichment (ARTE), and analysis of total serum IgE and IgG before and after initiation of ETI. Results: Mean Ki-67 expression in antigen-specific CD154 (+) T cells against P. aeruginosa, A. fumigatus, S. apiospermum and C. albicans, but not S. aureus, mean total serum IgG and mean total serum IgE decreased significantly after initiation of ETI. No correlation was found to change in sputum microbiology of the examined pathogens. Mean BMI and FEV1 increased significantly. Conclusion: HEMT is associated with decreased antigen-specific CD154 (+) T cell proliferation activity in our cohort, independent of findings in sputum microbiology of the examined pathogens. Together with the observed clinical improvement and the decrease in total IgE and IgG, this indicates effects due to CFTR restoration on CD154 (+) T cells by ETI and a reduction of B cell activation with subsequent lower immunoglobulin synthesis under HEMT therapy. These results endorse earlier evidence of CFTR dysfunction in T and B cells leading directly to aberrant immune responses with hyperinflammation. [ABSTRACT FROM AUTHOR]

Background Secretory IgA (sIgA) content of breastmilk in the first postpartum month is a reflection of the pregnant woman's immune response to environmental antigen exposure. The role of secretory IgA in breastmilk is to protect and support the development of the neonatal immune response in early life. Objective To examine possible factors associated with sIgA levels in breastmilk and colostrum, including environmental exposure, food consumed, maternal history of atopy, and the appearance of allergic symptoms in infants. As a secondary objective, we determined the association between infant factors (IgE, exposure to cigarette smoke) and maternal factors (sIgA, maternal allergies) with infant allergies. Methods This prospective cohort study of 80 postpartum mothers and their infants was conducted at Sultan Agung Islamic Hospital, Semarang. We collected maternal colostrum on the second or third postpartum day and mature milk between the 22nd to 25th postpartum day. Exposure factors to mothers and infants in the final trimester of pregnancy up to one month postpartum was recorded through a questionnaire and home visits. The infant’s IgE level was measured at 4 months of age. Results Mean colostrum sIgA was 108.9 (SD 16.5) mg/dL (95%CI 97.9 to 121.1 mg/dL) and mean mature milk sIgA was 94.1 (SD 23.9) mg/dL (95%CI 89.1 to 99.2 mg/dL). Mean colostrum sIgA levels were higher in mothers exposed to cigarette smoke [119.1 (SD 1.7) vs. 92.9 (SD 1.5) mg/dL; P=0.026] and frequent infections [128.2 (SD 1.7) vs. 95.9 (SD 1.6) mg/dL; P=0.007] compared to that in unexposed mothers. Mean colostrum sIgA was also higher in mothers with atopic allergy than in those without (136.8 mg/dL vs. 99.3 mg/dL; p=0.017) and in mothers of infants with IgE levels >29 IU/ml than in mothers of infants with IgE levels 136.8 mg/dL) was not associated with allergies in the infants (P=0.269). Conclusions Maternal atopic allergy and frequent infections are associated with increased colostrum sIgA levels. Breastmilk sIgA levels are not associated with allergies in the infant. Maternal exposure to antigens may stimulate the production of specific breastmilk sIgA.

Abstract Background Pediatric Mastocytosis is a rare and heterogeneous disease, characterized by accumulation of mast cells in the skin (Cutaneous Mastocytosis) and/or, less frequently, in other organs, mainly liver, spleen, bone marrow, lymph nodes and gastrointestinal tract (Systemic Mastocytosis). Patients affected by Systemic Mastocytosis show symptoms caused by a massive release of mast cell mediators: itching, flushing, abdominal pain, generalized weakness, fatigue and neuropsychiatric disorders. Moreover, children with Systemic Mastocytosis are at greater risk of anaphylactic/anaphylactoid reactions, often poorly controlled by the conventional therapy with antihistamines, mast cells stabilizers and steroids. As a result, children affected by Systemic Mastocytosis have a poor quality of life and suffer the consequence of prolonged steroidal treatment. Case presentation A child with Systemic Mastocytosis and severe symptoms, refractory to symptomatic and steroidal therapy, has been successfully treated with Omalizumab, an anti-IgE monoclonal antibody usually employed in allergic patients with severe asthma and orticaria. The onset of clinical benefit of Omalizumab therapy was extraordinarily rapid, but proved to be strictly dependent on drug administration. The child has become completely and steadily asymptomatic. No other anaphylactic episodes have been reported. Steroid treatment could be definitively withdrawn after the second dose of Omalizumab, and all the other medications were later reduced. Twenty months after beginning, Omalizumab therapy is still ongoing with good symptomatology control; no side effects have been observed so far. Conclusions In our experience, Omalizumab is an effective treatment for children affected by Systemic Mastocytosis not responding to conventional medical treatments. The main strengths of this therapy are its rapid and extraordinary efficacy to control the severe mast cells mediator-related symptoms, the lack of side effects and its steroid-sparing effect. However, more extensive and controlled studies in pediatric patients affected by Systemic Mastocytosis are needed to substantiate these promising findings.

Background: Allergic rhinitis (AR) is characterized by the increased sensitivity of the nasal mucosa to allergens and has a significant impact on life quality. There is promising evidence that biomarkers can help in the diagnosis, treatment, and follow-up of patients with AR. Diamine oxidase (DAO) is one of the enzymes responsible for the breakdown of histamine, the primary mediator of allergies. Objective: To investigate the significance of DAO as a useful biomarker for diagnosis and the severity of AR. Methods: In this case-control study, 24 patients and 24 healthy controls were recruited and their serum DAO levels, total IgE levels (using ELISA), blood eosinophil count, and percentage (using complete blood cell count) were measured. The sino-nasal outcomes test-22 (SNOT-22) questionnaire was used to assess the severity of symptoms in patients. The Receiver Operating Characteristic (ROC) analysis was used to assess the predictive power of DAO level for the diagnosis of AR. The relationship between DAO and disease severity, as well as other AR-related clinical factors, were also investigated. Results: DAO levels were lower in AR patients compared with the controls. The DAO level did not significantly correlate with the severity of AR according to the Allergic Rhinitis and its Impact on Asthma (ARIA) score, though it was lower in patients with persistent or moderate to severe symptoms. The total IgE, eosinophil percentage, and SNOT-22 score all had an inverse relationship with DAO. Moreover, DAO was significantly associated with the diagnosis of AR, with an Area under the ROC Curve (AUC) of 0.771, a sensitivity of 75%, and a specificity of 62.5%. Conclusion: DAO might be a valuable biomarker in the diagnosis of allergic rhinitis.

Abstract Introduction Asthma is a heterogenous disease with various phenotypes that is characterized by airway limitation due to bronchospasm and airway inflammation associated with excessive mucus secretion. Eosinophilic asthma subtype is described as a late onset asthma that presents with more severe respiratory symptoms, and with sputum eosinophilia ≥ 3%. In the current study, we aimed to identify the difference in the clinical and demographic characteristics between eosinophilic and non-eosinophilic asthma subtypes and to determine predictors of eosinophilic asthma. Materials and methods One hundred bronchial asthma patients with age ≥ 18 years were divided into two groups according to sputum eosinophilia. All patients were subjected to medical history, Asthma Control Test (ACT), spirometry, serum IgE level, skin prick testing (SPT), and nasal endoscopy to detect nasal polyposis and allergic signs. Results No statistical difference was found between eosinophilic and non-eosinophilic asthma patients regarding age, gender, and body mass index. Patients with sputum eosinophilia had more severe obstruction by spirometry, and positive SPT to food allergens, pollens, and latex with statistical significance (p values 0.001, 0.016, and 0.017 respectively). Additionally, patients with sputum eosinophilia had lower ACT score, higher serum IgE level and higher serum eosinophil count. Total IgE had the highest diagnostic accuracy for discrimination of sputum eosinophilia among asthma patients. Pollen allergy and the severity of airway obstruction by spirometry were independent predictors of eosinophilic asthma. Conclusion Patients with eosinophilic asthma had more severe airway obstruction, lower ACT scores, higher serum IgE level, and serum eosinophil count. Pollen allergy and obstructive pattern by spirometry were independent predictors of eosinophilic asthma.

The allergic asthma phenotype is characterized by a T helper type 2 (Th2) immune response, based on Immunoglobulin E (IgE)-mediated type 1 hypersensitivity reactions. Total IgE is the sum of all IgE types produced by the human body and is used as a biomarker of inflammation in asthma. We analysed data collected in 143 asthma cases (median age 42.1 years) from the general Italian population (GEIRD survey; 2008–2010) to identify single nucleotide polymorphisms (SNPs) in candidate genes that are associated with total IgE in adult subjects with asthma. These patients reported respiratory symptoms in response to perennial allergens and provided data on 166 SNPs tagging 50 candidate genes or gene regions. Replication of the statistically significant results was performed in 842 asthma cases from other European countries (ECRHS II survey; 1998–2002). SNP rs549908 in interleukin 18 (IL18) gene was significantly associated with total IgE in GEIRD, and this result was replicated in ECRHS II. SNP rs1063320 in the human leukocyte antigen G (HLA-G) gene was identified in GEIRD, but this association was not replicated in ECRHS II. Further investigating IL18 and its biological pathways could be important for developing new therapeutic targets, due to its involvement in inflammatory response processes. [ABSTRACT FROM AUTHOR]

Le système immunitaire de l'œil présente des caractéristiques particulières et spécifiques. En effet, cet organe bénéficie d'un statut particulier dit de privilège immun qui permet, via différents mécanismes, de limiter la réponse inflammatoire immunitaire afin de protéger la vision. Les atteintes pathologiques oculaires sont de ce fait souvent localisées. De plus, les manifestations cliniques de ces pathologies sont parfois peu spécifiques, ce qui rend leur diagnostic difficile. L'exploration biologique du système immunitaire de l'œil est donc une aide précieuse dans le diagnostic et le suivi de certaines de ces pathologies. Sera notamment présenté ici l'intérêt du dosage dans les prélèvements oculaires de l'interleukine (IL)-10 et celui du ratio IL-10/IL-6 pour le diagnostic et le suivi du lymphome oculaire, des cytokines pro-inflammatoires pour les uvéites et des IgE totales pour les conjonctivites allergiques. The immune system of the eye has special and specific characteristics. Indeed, this organ benefits from a special status called immune privilege which allows, via different mechanisms, to limit the immune inflammatory response in order to protect vision. Ocular pathologies are therefore often localized. In addition, the clinical manifestations of these pathologies could be non-specific, which makes their diagnosis difficult. The biological exploration of the immune system of the eye is therefore a valuable help in the diagnosis and monitoring of some of these pathologies: this article presents in particular the interest of interleukin (IL)-l0 assay and the IL-I0/IL-6 ratio in ocular samples for the diagnosis and monitoring of intraocular lymphoma, of pro-inflammatory cytokines for uveitis and of total IgE for allergic conjunctivitis. [ABSTRACT FROM AUTHOR]

The response of severe chronic spontaneous urticaria (CSU) to omalizumab largely depends on the autoimmune or autoallergic endotype of the disease. Whether thyroid autoimmunity may predict omalizumab response along with total IgE in CSU is still unclear. Three hundred and eighty-five patients (M/F 123/262; mean age 49.5 years; range 12–87 years) with severe CSU were studied. Total IgE levels and thyroid autoimmunity (levels of anti-thyroid peroxidase [TPO] IgG) were measured before omalizumab treatment. Based on the clinical response, patients were divided into early (ER), late (LR), partial (PR) and non (NR) responders to omalizumab. Thyroid autoimmunity was detected in 92/385 (24%) patients. Altogether, 52%, 22%, 16% and 10% of patients were ER, LR, PR and NR to omalizumab, respectively. Response to omalizumab was not associated with thyroid autoimmunity (p = 0.77). Conversely, we found a strongly positive association between IgE levels and omalizumab response (p < 0.0001); this association was largely driven by early response (OR = 5.46; 95% CI: 2.23–13.3). Moreover, the predicted probabilities of early response strongly increased with increasing IgE levels. Thyroid autoimmunity alone cannot be used as a clinical predictor of omalizumab response. Total IgE levels remain the only and most reliable prognostic marker for omalizumab response in patients with severe CSU. [ABSTRACT FROM AUTHOR]

Background: In the 5 years that have passed since the publication of the 2018 International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (ICAR-Allergic Rhinitis 2018), the literature has expanded substantially. The ICAR-Allergic Rhinitis 2023 update presents 144 individual topics on allergic rhinitis (AR), expanded by over 40 topics from the 2018 document. Originally presented topics from 2018 have also been reviewed and updated. The executive summary highlights key evidence-based findings and recommendation fromthe full document. Methods: ICAR-Allergic Rhinitis 2023 employed established evidence-based reviewwith recommendation (EBRR) methodology to individually evaluate each topic. Stepwise iterative peer review and consensuswas performed for each topic. The final document was then collated and includes the results of this work. Results: ICAR-Allergic Rhinitis 2023 includes 10 major content areas and 144 individual topics related to AR. For a substantial proportion of topics included, an aggregate grade of evidence is presented, which is determined by collating the levels of evidence for each available study identified in the literature. For topics in which a diagnostic or therapeutic intervention is considered, a recommendation summary is presented, which considers the aggregate grade of evidence, benefit, harm, and cost. Conclusion: The ICAR-Allergic Rhinitis 2023 update provides a comprehensive evaluation of AR and the currently available evidence. It is this evidence that contributes to our current knowledge base and recommendations for patient evaluation and treatment. [ABSTRACT FROM AUTHOR]

Introduction: This paper reports the study of a combined genetic and biomarker panel for assessing the risk of development of different phenotypes of atopic dermatitis (AD) in children: alone and combined with other atopic disorders (AtD) - allergic rhinitis/rhino-conjunctivitis (AR/ARC) and bronchial asthma (BA). The aim was to establish a personalized diagnostic multi-marker panel for assessing the developmental risk of different AD phenotypes in children combining single nucleotide polymorphism (SNP) rs_7927894 filaggrin (FLG) genotype variants, serum levels of total immune globulin E (IgE), cutaneous T-cell attracting chemokine (CTACK/CCL27) and thymus and activation regulated chemokine (TARC/CCL17). Material and methods: The study recruited patients aged 3-18 years old: 39 atopic patients to the main group and 47 non-atopic patients to the control group. All the patients were tested for SNP variants of rs_7927894 FLG and serum concentrations of total IgE, CTACK/CCL27 and TARC/CCL17. Results: Within AD alone phenotype patients we detected the following significant risk ratios: cytosine\thymine (C/T) rs_7927894 FLG [odds ratio (OR) = 4.14, p < 0.05], total IgE > 173 IU/ml (OR = 8.98, p < 0.001), CTACK/CCL27 > 3658.5 pg/ml (OR = 5.64, p < 0.01). Atopic disorders combined with other AtD phenotype: C/T rs_7927894 FLG (OR = 2.88, p < 0.05), total IgE > 213 IU/ml (OR = 136.7, p < 0.001), CTACK/CCL27 > 4308.8 pg/ml (OR = 7.40, p < 0.001). With AD combined with other AtD collated to AD alone - total IgE > 1001 IU/ml (OR = 16.0, p < 0.001). TARC/CCL17 had no significant differences among main and control groups. Conclusions: Cytosine\thymine rs_7927894 FLG variant combined with cut-off serum IgE and CTACK/CCL27 levels is a novel significant personalized multi-marker panel for assessing the risk of development of the different AD phenotypes in children. [ABSTRACT FROM AUTHOR]

Background: Together with impaired mucociliary clearance, lung disease in cystic fibrosis (CF) is driven by dysregulation of innate and adaptive immunity caused by dysfunctional CFTR (Cystic Fibrosis Transmembrane Conductance Regulator), leading to airway infection and hyperinflamma-tion. The highly effective CFTR modulator therapy (HEMT) elexacaftor/tezacaftor/ivacaftor (ETI) generates substantial improvements in clinical outcomes of people with CF (pwCF) by restoration of CFTR activity. Aberrant immune responses of lymphocytes due to CFTR dysfunction has been described in the past, but not the effects of CFTR restoration by HEMT on these cells. We aimed to examine the effect of ETI on the proliferative activity of antigen-specific CD154 (+) T cells against bacterial and fungal species relevant in CF and on total IgG and IgE as markers of B cell adaptive immunity.Methods: We performed ex vivo analyses of Ki-67 expression in antigen-specific CD154 (+) T cells against Pseudomonas aeruginosa, Staphylococcus aureus, Aspergillus fumigatus, Scedosporium apiospermum and Candida albicans from 21 pwCF by cytometric assay based on antigen-reactive T cell enrichment (ARTE), and analysis of total serum IgE and IgG before and after initiation of ETI.Results: Mean Ki-67 expression in antigen-specific CD154 (+) T cells against P. aeruginosa, A. fumigatus, S. apiospermum and C. albicans, but not S. aureus, mean total serum IgG and mean total serum IgE decreased significantly after initiation of ETI. No correlation was found to change in sputum microbiology of the examined pathogens. Mean BMI and FEV1 increased significantly.Conclusion: HEMT is associated with decreased antigen-specific CD154 (+) T cell proliferation activity in our cohort, independent of findings in sputum microbiology of the examined pathogens. Together with the observed clinical improvement and the decrease in total IgE and IgG, this indicates effects due to CFTR restoration on CD154 (+) T cells by ETI and a reduction of B cell activation with subsequent lower immunoglobulin synthesis under HEMT therapy. These results endorse earlier evidence of CFTR dysfunction in T and B cells leading directly to aberrant immune responses with hyperinflammation.

Background: Total immunoglobulin E (IgE) analysis is a common tool in allergy diagnosis. Suggested reference values for IgE are divergent and sometimes based on outdated assay methods. We aimed to validate the published reference values (geometric mean [GM]: 13.2 kU/L, upper limit of normal [ULN], 114 kU/L) shown in an Uppsala cohort from 1974 using Phadebas IgE PRIST, and the suggested clinical threshold of 100 kU/L (Zetterström and Johansson 1981). Methods: Immunoglobulin E was measured in two Uppsala cohorts from 1997 (Blood bank) and 2011 to 2013 (the European community respiratory health survey part III [ECRHS III]) using ImmunoCAP™ Total IgE. For the reference value calculations, exclusion criteria were atopy (both cohorts), doctor's diagnosis of asthma and self-reported allergy (hay fever, rhinitis, rash) (only ECRHS III). Upper limit of normal was defined as mean + 2 standard deviations (SD) calculated using log-transformed values and back-transformation of the ULN prior to presentation. Common imputation methods for results below the assay range were evaluated. Results: The average GM was 14.2 kU/L (Blood bank, n = 63; imputation method range: 16.9-17.4 kU/L; ECRHS III, n = 113: 10.7-11.6 kU/L) and the overall mean ULN was 118 kU/L (Blood bank: 113-130 kU/L; ECRHS III: 104-128 kU/L). The clinical sensitivity and specificity of the 100 kU/L IgE threshold were 37.8 and 94.3% for atopy, 34.9 and 89.5% for doctor's diagnosis of asthma, and 24.5 and 97.3% for any self-reported allergy (ECRHS III). Conclusion: The calculated ULN values were similar between the cohorts. We conclude that the total IgE reference values shown for Uppsala subjects from 1974 are still valid and suitable also for the ImmunoCAP Total IgE assay. The 100 kU/L threshold for total IgE had a low sensitivity but high specificity for atopy, asthma, and allergy. [ABSTRACT FROM AUTHOR]

Background/aim: Animal dander is one of the most common respiratory allergens in children, and there is evidence that cat sensitivity is a risk factor for asthma and allergic rhinitis. In this study, it was aimed to evaluate children with cat sensitivity and to identify their demographic and clinical characteristics. Materials and methods: Patients who were found to be sensitive to cats following skin prick tests performed in our allergy clinic over a period of one year (and two control groups), were included in the study. Patients in the study and control groups filled in a questionnaire including demographic and clinical characteristics. Results: The prevalence of cat sensitivity in our allergy clinic was 6% (182/3033). The most common diagnoses in patients were 41.8% allergic rhinitis, 25.8% asthma, and 13.2% allergic rhinitis + asthma. Allergic rhinitis symptoms were the most prevalent symptom associated with cat contact (29.4%), whereas 28% of the patients were asymptomatic. Only 17.3% had a cat at home and 13.4% had cat exposure apart from home but having a cat at home was significantly higher than the control groups (p < 0.05). Eosinophilia was present in 54.6% of the patients, and 17.3% had blood tIgE levels of >1000 IU/mL. Eosinophilia and tIgE levels were significantly higher than both control groups (p < 0.05). Conclusion: Cat ownership can affect the development of cat sensitivity but the majority of patients with cat sensitivity are not cat owners. Elevated tIgE levels (> 1000 IU/mL) may be associated with cat sensitivity, these patients should be evaluated for cat sensitivity, even if they do not report symptoms with cat contact. [ABSTRACT FROM AUTHOR]

Background: It is important and expected of laboratories to provide updated reference intervals to the clinician. As no recent publications report adult total IgE reference intervals on a Scandinavian population, the aim of our study was therefore to provide an estimate on healthy Norweigian adults. Methods: A reference interval study was conducted in accordance to CLSI guidelines. Samples were collected from n = 252 presumably healthy adult participants enrolled through the regional blood donation program. Total IgE measurements were performed on the ImmunoCAPTM platform (Thermo Fisher Diagnostics) traceable to the WHO-reference standard (75/502) for total IgE measurements. Results: An upper 95% total IgE reference limit was estimated to 302 kU/L (90% CI 177-388 kU/L), and the 97.5% percentile was estimated to 391 kU/L (90% CI 344-560 kU/L). No significant differences were found between participants who self-reported having an allergic disease and participants who did not self-report having an allergic disease. Conclusion: Our results and other recent publications find markedly higher values than adult reference intervals established four decades ago which still remain widely used by clinical laboratories. We therefore recommend total IgE reference intervals should be critically reviewed and updated. [ABSTRACT FROM AUTHOR]

Background Secretory IgA (sIgA) content of breastmilk in the first postpartum month is a reflection of the pregnant woman's immune response to environmental antigen exposure. The role of secretory IgA in breastmilk is to protect and support the development of the neonatal immune response in early life. Objective To examine possible factors associated with sIgA levels in breastmilk and colostrum, including environmental exposure, food consumed, maternal history of atopy, and the appearance of allergic symptoms in infants. As a secondary objective, we determined the association between infant factors (IgE, exposure to cigarette smoke) and maternal factors (sIgA, maternal allergies) with infant allergies. Methods This prospective cohort study of 80 postpartum mothers and their infants was conducted at Sultan Agung Islamic Hospital, Semarang, Central Java. We collected maternal colostrum on the second or third postpartum day and mature milk between the 22nd to 25th postpartum day. Exposure factors to mothers and infants in the final trimester of pregnancy up to one month postpartum was recorded through a questionnaire and home visits. The infant's IgE level was measured at 4 months of age. Results Mean colostrum sIgA was 108.9 (SD 16.5) mg/dL (95%CI 97.9 to 121.1 mg/dL) and mean mature milk sIgA was 94.1 (SD 23.9) mg/dL (95%CI 89.1 to 99.2 mg/dL). Mean colostrum sIgA levels were higher in mothers exposed to cigarette smoke [119.1 (SD 1.7) vs. 92.9 (SD 1.5) mg/dL; P=0.026] and frequent infections [128.2 (SD 1.7) vs. 95.9 (SD 1.6) mg/dL; P=0.007] compared to that in unexposed mothers. Mean colostrum sIgA was also higher in mothers with atopic allergy than in those without (136.8 mg/dL vs. 99.3 mg/dL; P=0.017) and in mothers of infants with IgE levels >29 IU/mL than in mothers of infants with IgE levels <29 IU/mL (136.8 vs. 101.2 mg/mg/dL; P=0.045). Elevated colostrum sIgA (>136.8 mg/dL) was not associated with allergies in the infants (P=0.269). Conclusions Maternal atopic allergy and frequent infections are associated with increased colostrum sIgA levels. Breastmilk sIgA levels are not associated with allergies in the infant. Maternal exposure to antigens may stimulate the production of specific breastmilk sIgA. [ABSTRACT FROM AUTHOR]

Abstract Background Immunoglobulin E (IgE) is the least prevalent antibody type; it plays a key role in host immunity against parasitic infections and allergic diseases. Association between IgE deficiency and higher malignancy rates has been suggested in many studies. Objectives The goal of our study was to determine the prevalence of ultra-low total IgE levels and their variations according to sex and age among the Egyptian population. Methodology This multicenter retrospective cross-sectional study included serum total IgE and CBC records of 1099 children and 993 adults recruited from private and public hospitals in Egypt between 2015 and 2021. Total IgE levels were classified into ultra-low, normal, high, and very high. Results Of all included subjects, 0.8% had ultra-low IgE levels and 74.4% had normal IgE levels. High and very high serum total IgE levels were 24.1% and 0.7%, respectively. IgE levels were significantly higher among adults than children 45 (16.5–113.25) IU/ml vs. 20 (10–75) IU/ml; p

Abstract Background It is important and expected of laboratories to provide updated reference intervals to the clinician. As no recent publications report adult total IgE reference intervals on a Scandinavian population, the aim of our study was therefore to provide an estimate on healthy Norweigian adults. Methods A reference interval study was conducted in accordance to CLSI guidelines. Samples were collected from n = 252 presumably healthy adult participants enrolled through the regional blood donation program. Total IgE measurements were performed on the ImmunoCAPTM platform (Thermo Fisher Diagnostics) traceable to the WHO‐reference standard (75/502) for total IgE measurements. Results An upper 95% total IgE reference limit was estimated to 302 kU/L (90% CI 177–388 kU/L), and the 97.5% percentile was estimated to 391 kU/L (90% CI 344–560 kU/L). No significant differences were found between participants who self‐reported having an allergic disease and participants who did not self‐report having an allergic disease. Conclusion Our results and other recent publications find markedly higher values than adult reference intervals established four decades ago which still remain widely used by clinical laboratories. We therefore recommend total IgE reference intervals should be critically reviewed and updated.

BackgroundCritical examination of the quality and validity of available allergic rhinitis (AR) literature is necessary to improve understanding and to appropriately translate this knowledge to clinical care of the AR patient. To evaluate the existing AR literature, international multidisciplinary experts with an interest in AR have produced the International Consensus statement on Allergy and Rhinology: Allergic Rhinitis (ICAR:AR).MethodsUsing previously described methodology, specific topics were developed relating to AR. Each topic was assigned a literature review, evidence-based review (EBR), or evidence-based review with recommendations (EBRR) format as dictated by available evidence and purpose within the ICAR:AR document. Following iterative reviews of each topic, the ICAR:AR document was synthesized and reviewed by all authors for consensus.ResultsThe ICAR:AR document addresses over 100 individual topics related to AR, including diagnosis, pathophysiology, epidemiology, disease burden, risk factors for the development of AR, allergy testing modalities, treatment, and other conditions/comorbidities associated with AR.ConclusionThis critical review of the AR literature has identified several strengths; providers can be confident that treatment decisions are supported by rigorous studies. However, there are also substantial gaps in the AR literature. These knowledge gaps should be viewed as opportunities for improvement, as often the things that we teach and the medicine that we practice are not based on the best quality evidence. This document aims to highlight the strengths and weaknesses of the AR literature to identify areas for future AR research and improved understanding.

In this study, it was aimed to evaluate asthma patients who applied to the chest diseases outpatient clinic in terms of allergies. 240 asthma patients over the age of 18 who applied to the chest diseases outpatient clinic with the diagnosis of asthma were evaluated retrospectively. No statistical difference was obtained between the education status, employment status, presence of additional disease, presence of chronic disease, skin prick test and Total IgE results in terms of asthma severity and AKT. While no correlation was obtained between AKT and eosinophil percentage; asthma severity was associated with the eosinophil percentage (p=0.039). According to the results of the skin prick test, the most common allergens were detected to be house dust, pollen and animal feather. Early detection of allergy in asthma patients is very important for the follow-up and treatment of patients. While the eosinophil percentage provides benefits in determining future risks in asthma, the Total IgE result is a test that guides to anti-IgE (Omalizumab) therapy. In the patients with severe asthma which is resistant to treatment, peripheral blood eosinophils and Total IgE should be checked, and appropriate patients should be referred to advanced centers. [ABSTRACT FROM AUTHOR]

Introduction: An atopic status assessment (skin prick test or specific immunoglobulin (sIgE)) in asthmatic children is considered a milestone in identifying potential risk factors and triggers provoking loss of asthma control and asthma exacerbation. Objective: The study aims to perform a comparative analysis of different laboratory methods for a serological assessment of an atopic status in asthma and respiratory allergies in children. Material and methods: A total of 86 children were included, all of whom were diagnosed with bronchial asthma, aged from 5 to 17 years and screened for total IgE level using enzyme-linked immunosorbent assay (ELISA). In 48 randomly selected children, we performed a semi-quantitative serological in vitro assessment of the specific IgE antibodies against food and aeroallergen, using two different laboratory methods—Euroimmun Immunoblot and ImmunoCAP (Phadiatop/fx5). Results: In 70% of the children with a history of allergies, and 65.3% without clinically manifested allergies, multiscreen test ImmunoCAP Phadiatop/fx5 showed positivity and confirmed atopy. Our results showed a significant moderate to strong correlation between multiscreen ImmunoCAP Phadiatop/fx5, and Euroimmun specific IgE titers against aero-allergens—cats, mites, tree mix and food allergens—soy, wheat (р = 0.006), rice, р = 0.090), apple р = 0.007) and peanut. A sensitivity of 63% and specificity of 73.5% was observed for EUROIMMUN Pediatric (food allergens, IgE titer > 1) compared with the gold standard ImmunoCap/fx5. The mean value of total IgE is significantly higher in children with asthma and concomitant with allergic rhinitis compared to those without allergic rhinitis (mean 202.52 U/mL, IQR 102.50 (24.20–363.95) vs. 316.68, IQR 261.00 (109.20–552.50), p = 0.005). Conclusion: Establishing the spectrum of the most common respiratory and food allergens is an essential factor for maintaining asthma control, both through a strategy to avoid allergen exposure and by developing a recommendation plan. The immunoblotting technique is easily applicable in daily clinical and laboratory practice. It is also a cost-effective and reliable alternative to the “gold standard” ImmunoCAP Phadiatop/fx5 in diagnosing atopy in children.

BackgroundThe gold standard to diagnose food allergy (FA) is a double-blind, placebo-controlled food challenge (OFC), even if it shows potential risk of severe allergic reactions for the patient and is time-consuming. Therefore, easier, and less invasive methods are needed to diagnose FA and predict the tolerance, changing the clinical practice.AimThe main aim of this study was to assess whether the total IgE values at the diagnosis of FA were associated with the duration of the tolerance acquisition and thus of the food elimination diet.MethodsWe retrospectively analyzed the medical records of 40 patients allergic to milk or egg who performed an OFC for the reintroduction of the causal food at the Pediatric Allergy and Respiratory Unit of the University of Chieti from January 2018 to December 2020.ResultsWe found a positive association of total serum IgE with the elimination diet duration (β = 0.152; CI, 95% 0.04–0.27) after adjusting for age, sex, and type of allergy (milk or egg). We also showed a significant correlation (r = 0.41 and p-value = 0.007) between the total IgE values and the duration of the elimination diet and a significant correlation between the casein specific IgE values at diagnosis of FA and the severity of the clinical presentation (r = 0.66; p-value 0.009).ConclusionTotal serum IgE at baseline, along with the downward trend of food-specific IgE levels (to milk or egg), may be useful in the prognostication of natural tolerance acquisition.

Background: Laboratory biomarkers to estimate the severity of coronavirus disease 2019 (COVID‐19) are crucial during the pandemic since resource allocation must be carefully planned. Aims: To evaluate the effects of basal serum total immunoglobulin E (IgE) levels and changes in inflammatory parameters on the clinical progression of patients hospitalised with COVID‐19. Methods: Patients hospitalised with confirmed COVID‐19 were included in the study. Laboratory data and total IgE levels were measured on admission. Lymphocyte, eosinophil, ferritin, d‐dimer and C‐reactive protein parameters were recorded at baseline and on the 3rd and 14th days of hospitalisation. Results: The study enrolled 202 patients, of which 102 (50.5%) were males. The average age was 50.17 ± 19.68 years. Of the COVID‐19 patients, 41 (20.3%) showed clinical progression. Serum total IgE concentrations were markedly higher (172.90 (0–2124) vs 38.70 (0–912); P < 0.001) and serum eosinophil levels were significantly lower (0.015 (0–1.200) vs 0.040 (0–1.360); P = 0.002) in clinically worsened COVID‐19 patients when compared with stable patients. The optimal cut‐off for predicting clinical worsening was 105.2 ng/L, with 61% sensitivity, 82% specificity, 46.3% positive predictive value and 89.2% negative predictive value (area under the curve = 0.729). Multivariable analysis to define risk factors for disease progression identified higher total IgE and C‐reactive protein levels as independent predictors. Conclusions: Our single‐centre pilot study determined that total IgE levels may be a negative prognostic factor for clinical progression in patients hospitalised due to COVID‐19 infection. Future studies are required to determine the impact of individuals' underlying immune predispositions on outcomes of COVID‐19 infections. [ABSTRACT FROM AUTHOR]

Background: High serum IgE level in atopic children usually implies a highly sensitized condition. However, there is a subgroup of atopic children for whom a specific allergen cannot be identified. In this study, we analyzed follow-up data from these children. Methods: From March 2014 to July 2017, we recruited 14 atopic children with serum total IgE level higher than 500 Ku/L, but with no specific allergen identified by repeated MAST tests initially. Follow-up studies of specific IgE were conducted by the OPTIGEN MAST Allergy test and ImmunoCAP assays (Thermo Fisher Scientific/Phadia), while total IgE and specific IgG were measured by ImmunoCAP. Results: The patients were aged from 2 to 17 y/o. The follow-up MAST tests showed significantly positive results in 10 patients. There were no significant differences in any of the clinical characteristics between the MAST-positive and MAST-negative groups. In the MAST-negative group, five allergen-specific IgE antibodies, including those for cockroach, Euroglyphus maynei, Blomia tropicalis, shrimp, and crab, were strongly predictive of negative ImmunoCAP results, according to ROC (Receiver operating characteristic curve) analysis of the AUC (Area under the Curve of ROC) (0.70–0.95), with significance set at p