Nasal epithelial gene expression and total IgE in children and adolescents with asthma.

BACKGROUND: Little is known about nasal epithelial gene expression and total IgE in youth. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Our findings for nasal epithelial gene expression support neuroimmune coregulation of total IgE in youth with asthma.

Gene-based association study of rare variants in children of diverse ancestries implicates TNFRSF21 in the development of allergic asthma.

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Predicting the Speed of Response to Omalizumab in Chronic Spontaneous Urticaria.

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.

Establishment of a homogeneous chemiluminescence immunoassay for cat dander sIgE antibody detection.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Interpreting epidemiologic distribution of total and specific IgE levels for food allergy in Southern China from 2004 to 2023: understanding the mechanisms and focusing on prevention.

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.

Association of serum total IgE and allergen-specific IgE with insulin resistance in adolescents: an analysis of the NHANES database.

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.

Anti-TPO IgG/Total IgE Ratio: Biomarker for Omalizumab Response Prediction in Chronic Spontaneous Urticaria.

BACKGROUND: According to recently published data, low total IgE, elevated IgG-anti-TPO, and a high IgG-anti-TPO/total IgE ratio are good biomarkers for subtype IIb autoimmune chronic spontaneous urticaria (CSU), which is frequently refractory to antihistamines and omalizumab. OBJECTIVES: The aim of the study was to evaluate IgG-anti-TPO/total IgE ratio's utility in omalizumab response prediction. METHODS: Retrospective study of CSU patients treated with omalizumab at a UCARE between January 2009 and February 2022. Patients were grouped according to response in the first 16 weeks of treatment: responders UAS7 < 7 versus partial/non-responders UAS7≥7. Total IgE, IgG-anti-TPO, and IgG-anti-TPO/total IgE ratio were compared. Other inflammatory biomarkers - eosinophils, basophils, C-reactive protein, erythrocyte sedimentation rate, and d-dimer - were analyzed. STATISTICAL ANALYSIS: SPSS® (v25.0), p < 0.05 statistically significant. RESULTS: Total of 175 patients, 140 (80%) women, median age 49 [9-88] years, mean CSU duration pre-omalizumab 5.6 ± 8.2 [0-54] years, omalizumab duration 3.2 ± 2.5 [0-12] years. 116 (66%) had angioedema, 77 (44%) inducible chronic urticaria, 60 (34%) atopy, 24 (14%) autoimmune disease. With omalizumab 300 mg q4 weeks, 69% were responders and 31% partial/non-responders. Although not reaching significant differences, mean total IgE values were lower and mean IgG-anti-TPO values were higher in partial/non-responders versus responders (152 vs. 242 kU/L, p = 0.207, and 38.3 vs. 25.7 U/mL, p = 0.408, respectively). A higher IgG-anti-TPO/total IgE ratio was significantly associated with poorer response to omalizumab (p = 0.040). A cut-off >0.154 increased 10 times the odd of poorer response [95% CI 4.62-22], AUC 0.872, p < 0.001, with 87.7% sensitivity, although the low specificity (22.4%) does not allow the assumption of response with values <0.154. Other laboratory biomarkers did not show significant differences between partial/non-responders versus responders. CONCLUSIONS: A high IgG-anti-TPO/total IgE ratio was a good biomarker of poor response to omalizumab in our CSU cohort, with a cut-off >0.154 increasing 10 times the odd of poorer response.

Exhaled nitric oxide is only an asthma-relevant biomarker among children with allergic sensitization.

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.

Biomarkers of Autoimmune Chronic Spontaneous Urticaria.

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). Some biomarkers are easily accessible but of low specificity; others are highly specific but more futuristic.

A survey of total IgE reference intervals reported by Scandinavian and British medical laboratories - a need for harmonisation.

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.

Association of blood total immunoglobulin E and eosinophils with radiological features of bronchiectasis.

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.

Comparative analysis of serum total IgE levels and specific IgE levels in children aged 6 to 9 years with tic disorder and normal children.

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.

Thyroid Autoimmunity in CSU: A Potential Marker of Omalizumab Response?

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.

Characteristics of children with cat sensitivity: a prospective cross-sectional study.

BACKGROUND: 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. 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). DISCUSSION: 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.

Specific IgE to Total IgE Ratio Does Not Improve Peanut Diagnostic Accuracy in Adults.

BACKGROUND: Peanut specific IgE (sIgE) can lead to false-positive results. OBJECTIVE: We aimed to assess whether peanut sIgE to total IgE (tIgE) ratio improves accuracy in predicting clinical reactivity to peanut compared to peanut sIgE alone, which has not been explored in the adult population so far. METHOD: A retrospective chart review was performed for adults who underwent peanut oral food challenge (OFC) and/or oral immunotherapy (OIT) at the Centre Hospitalier de l'Université de Montréal's allergy clinic between January 2017 and July 2021. Patients with positive peanut OFC and/or undergoing OIT were considered peanut-allergic. Patients with negative OFC were considered peanut-tolerant. Peanut sIgE to tIgE ratios were calculated and performance characteristics of the sIgE to tIgE ratio were compared to sIgE alone by using receiver operator characteristics curves. RESULTS: Forty-two patients were included (52% male) with a median age of 26 years (range 14-54). Forty-five percent had atopic dermatitis. Median sIgE levels were 2.64 kUA/L (range 0.1-100), median tIgE levels were 154 kUA/L (range 19-3,400), and median sIgE to tIgE ratio was 0.66% (range 0.04-38.3). Twenty-four patients (57%) were classified as peanut-allergic and 18 (43%) as peanut tolerant. The area under the curve for peanut sIgE was 0.921 compared to 0.926 for peanut sIgE/tIgE (p not statistically significant). CONCLUSIONS: We found that there was no significant benefit in using peanut sIgE to tIgE ratio over sIgE alone to predict peanut reactivity in an adult population. Larger prospective studies are needed to further confirm these findings.

Serum total IgE may be a biomarker among chronic pulmonary aspergillosis patients with elevated serum total IgE levels: A cohort study with pathological evaluations.

High serum total immunoglobulin E (IgE) levels have been reported in chronic pulmonary aspergillosis (CPA). However, researchers have not verified if they reflect the disease activity. We aimed to compare the serum total IgE levels in CPA cases with high serum IgE during an exacerbation or when stable and examined the IgE expression patterns in the lesions via immunofluorescence staining. From April 2016 to September 2019, we extracted CPA cases with elevated serum total IgE levels based on the criteria of the Infectious Diseases Society of America. We retrospectively analyzed serum total IgE levels and other parameters and eventually extracted 32 cases. The patients' serum total IgE levels were significantly higher in the exacerbation period than in the stable period (P < .0001). The median rate of change was 1.76 times (quartile 1.41-3.25). In addition, we used surgical specimens of CPA cases with high serum total IgE levels, normal serum total IgE CPA cases, and control surgical specimens and performed immunofluorescence staining with IgE, mast cell tryptase, CD138, and 4,6-diamidino-2-phenylindole. We observed multiple mast cells and plasma cells in the CPA cases regardless of the serum total IgE level. In contrast, multiple IgE-positive cells co-stained with tryptase were observed in CPA cases with high serum total IgE levels. This finding suggested that serum total IgE could serve as a biomarker for evaluating disease severity. Immunofluorescence staining suggested that IgE may play a role in pathogenesis through activation of mast cells by cross-linking in cases of CPA with high serum total IgE levels. LAY SUMMARY: High serum total IgE levels are common in chronic pulmonary aspergillosis. This novel study indicated that serum total IgE is a possible biomarker of the disease activity in the aforementioned condition. Immunofluorescence staining indicated a possible role of IgE in disease pathogenesis.

Investigation of Serum Total IgE and Eosinophil Levels in Different Allergic Diseases Together with the Study of Their Correlations with Various Possible Allergens in Mosul City.

Serum total IgE (tIgE) is frequently used in the diagnosis of allergic diseases in Mosul city and Iraq. However, neither normal nor elevated levels can exclude or confirm the diagnosis of these diseases. Here, we tried to evaluate the validity of tIgE in the diagnosis of allergic asthma(AS), allergic rhinitis(AR) and atopic dermatitis(AD) in a sample of Mosul population, to set up an optimum cut-off value for diagnosis of these diseases and to study its correlation with different parameters that might affect its level. 38 patients with AS, 27 with AR, 46 with AD and 45 healthy controls were included in this study. tIgE were determined by ELISA and compared between allergic diseases and controls. Blood eosinophilia was ascertained and correlated with tIgE levels. The geometric means of tIgE were 316.87 IU/ml (95% CI: 234.69 to 427.82) in AS, 262.07 IU/ml (95% CI:174.24 to 394.18) in AR and 270.48 IU/ml (95% CI:202.57 to 361.16) in AD compared to 16.90 IU/ml (95% CI:12.32 to 23.18) in healthy controls. tIgE in allergic diseases was significantly increased in comparison to healthy controls (P <.0001). Female gender influenced tIgE in AS, but not in AR or AD. tIgE predominated in younger age groups; however, no significant difference was found between younger and older groups. Optimum values for tIgE with best discriminative accuracy were 77 IU/ml for AS and 81 IU/ml for AR and AD. Eosinophils count appeared to be a useful adjunct, and correlate well with tIgE in the diagnosis of allergic diseases.

Pilot study for immunoglobulin E as a prognostic biomarker in coronavirus disease 2019.

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.

Predictor of buckwheat allergy in children based on challenge test results: a retrospective observational study in Japan.

Summary: Background. Buckwheat (BW) is a major food allergen and one of the leading causes of food-induced anaphylaxis in Japan. The standard method of diagnosing food allergy is the oral food challenge (OFC). The BW-specific IgE (BW-sIgE) value is used to assess BW allergy but its utility is limited. Aim. The aim of the present study was to identify factors with predictive value for the diagnosis of BW allergy using the OFC. Methods. We evaluated 37 patients who were classified into the positive or negative group according to their OFC results. Results. Ten patients (27.0%) showed objective or persistent, moderate, subjective symptoms during the OFC. The positive group had a significantly higher BW-sIgE/total IgE ratio than the negative group (p less than 0.001), but the total IgE (p = 0.139) and BW-sIgE (p = 0.130) did not differ significantly. Receiver operator characteristic (ROC) analysis showed that the BW-sIgE/total IgE ratio had a larger area under the curve (AUC, 0.885) than BW-sIgE (AUC, 0.667). The statistically optimal cut-off was 0.0058 for the BW-sIgE/total IgE ratio, which corresponded to a clinical sensitivity and specificity of 90.0% and 81.5%, respectively. Conclusions. BW-sIgE/total IgE ratio may be more useful predictor of BW OFC results than BWs-IgE.

Racial/ethnic differences in eligibility for asthma biologics among pediatric populations.

BACKGROUND: Asthma 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. OBJECTIVE: We investigated the association of blood parameters and asthma subtypes with asthma outcomes and examined population-specific eligibility for biologic therapies in minority pediatric populations. METHODS: Using 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. RESULTS: Race/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. CONCLUSIONS: We 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.