Total Serum IgE Research Articles

Assessing the predictive potential of ADAM8 for disease control in chronic rhinosinusitis with nasal polyps

BackgroundA disintegrin and metalloproteinase 8 (ADAM8) has been implicated in eosinophilic inflammation; however, its role in chronic rhinosinusitis with nasal polyps (CRSwNP) remains to be elucidated. This study aimed to investigate the predictive significance of ADAM8 levels in nasal secretions for the endotypes and disease control status of CRSwNP.MethodsA cohort comprising 120 CRSwNP patients and 45 healthy controls (HCs) was assembled, delineating 53 non-eosinophilic CRSwNP (neCRSwNP) and 67 eosinophilic CRSwNP (eCRSwNP) patients. Immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) were utilized to measure ADAM8 levels in nasal mucosal tissues and secretions from all participants. The receiver operating characteristic (ROC) curves and Pearson correlation analysis were employed to assess the predictive capability of ADAM8 levels in predictiving CRSwNP endotypes and disease control status.ResultsADAM8 levels in nasal secretions were elevated in CRSwNP patients compared to HCs, with a more pronounced increase observed in eCRSwNP patients. Elevated ADAM8 concentrations in nasal secretions were positively correlated with peripheral blood eosinophil counts and percentages, tissue eosinophil counts, serum total IgE, Lund–Mackay scores, and Lund-Kennedy scores. Ultimately, 103 CRSwNP patients completed the follow-up protocol, with 72 classified as the controlled group and 31 as the uncontrolled group. Uncontrolled CRSwNP patients exhibited significantly higher ADAM8 levels in nasal secretions compared to the controlled group. The ROC curves indicated that ADAM8 in nasal secretions exhibits robust discriminatory capacity for eCRSwNP and postoperative disease control status.ConclusionADAM8 in nasal secretions emerges as a potential novel biomarker for the prognostication of CRSwNP endotypes and the postoperative disease control status.

Arctiin Alleviates Atopic Dermatitis Against Inflammation and Pyroptosis Through Suppressing TLR4/MyD88/NF-κB and NLRP3/Caspase-1/GSDMD Signaling Pathways.

Atopic dermatitis (AD) is a prevalent skin condition worldwide. The immune response plays a crucial role in the pathogenesis of AD. Arctiin (ARC), a natural lignan, has been extensively investigated because of its anti-inflammatory, antioxidant, and anticancer properties. However, the impact of ARC on AD remains uncertain. Therefore, this study investigated the therapeutic effects of ARC in AD. AD-like lesions were induced in mice by applying 2,4-dinitrochlorobenzene (DNCB). The efficacy of ARC in AD was assessed by measuring skin lesion scores and thickness, pathological observation, and serum IgE concentrations. The expression of relevant proteins and genes in the back skin of the mice was assessed. Moreover, the TLR4/MyD88/NF-κB and NLRP3/Caspase-1/GSDMD signaling pathways were assessed in HaCaT cells stimulated with TNF-α and IFN-γ. ARC effectively alleviated AD-like dermatitis induced by DNCB in mice, reducing the skin thickness, mast cell infiltration in skin tissue, and serum total IgE levels. In addition, the expression of IL-1β and the mRNA transcription of TSLP and IFN-γ were downregulated. ARC also suppressed the TLR4/MyD88/NF-κB pathway, and molecular docking confirmed that ARC had exceptional binding properties with TLR4. Moreover, ARC ameliorated pyroptosis by inhibiting the activation of the nod-like receptor protein-3/Caspase-1/GSDMD cascade. ARC has remarkable anti-AD effects by inhibiting inflammation and pyroptosis through the TLR4/MyD88/NF-κB and NLRP3/Caspase-1/GSDMD signaling pathways. This suggests that ARC has potential as a new drug candidate for treating AD, which provides a novel approach to the clinical management of AD.

Fecal microbiota transplantation against moderate-to-severe atopic dermatitis: A randomized, double-blind controlled explorer trial.

Fecal microbiota transplantation (FMT) is a novel treatment for inflammatory diseases. Herein, we assess its safety, efficacy, and immunological impact in patients with moderate-to-severe atopic dermatitis (AD). In this randomized, double-blind, placebo-controlled clinical trial, we performed the efficacy and safety assessment of FMT for moderate-to-severe adult patients with AD. All patients received FMT or placebo once a week for 3 weeks, in addition to their standard background treatments. Patients underwent disease severity assessments at weeks 0, 1, 2, 4, 8, 12, and 16, and blood and fecal samples were collected for immunologic analysis and metagenomic shotgun sequencing, respectively. Safety was monitored throughout the trial. Improvements in eczema area and severity index (EASI) scores and percentage of patients achieving EASI 50 (50% reduction in EASI score) were greater in patients treated with FMT than in placebo-treated patients. No serious adverse reactions occurred during the trial. FMT treatment decreased the Th2 and Th17 cell proportions among the peripheral blood mononuclear cells, and the levels of TNF-α, and total IgE in serum. By contrast, the expression levels of IL-12p70 and perforin on NK cells were increased. Moreover, FMT altered the abundance of species and functional pathways of the gut microbiota in the patients, especially the abundance of Megamonas funiformis and the pathway for 1,4-dihydroxy-6-naphthoate biosynthesis II. FMT was a safe and effective therapy in moderate-to-severe adult patients with AD; the treatment changed the gut microbiota compositions and functions.

Characterizing Non-T2 Asthma: Key Pathways and Molecular Implications Indicative of Attenuated Th2 Response.

Non-Type 2 (non-T2) asthma is characterized by a lack of allergic sensitization and normal to low total IgE levels. We aimed to explore molecular mechanisms and pathways differentiating non-T2 from T2-high pediatric asthma. We analyzed peripheral blood RNA samples from 11 non-T2 and 17 T2-high pediatric asthma patients using bulk RNA sequencing. Differentially expressed genes (DEGs) were identified, followed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, and Protein-Protein Interaction (PPI) network construction. Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) were employed to explore significance of these DEGs. We utilized independent public datasets GSE145505 to validate our findings. We investigated Th cytokine profiles in an independent cohort of pediatric patients with non-T2 asthma (n = 38) and T2-high asthma (n = 64). We demonstrated that the total serum IgE levels of children with non-T2 asthma (128.4 ± 159.5IU/mL) was significantly lower than that of those with T2-high asthma (405.8 ± 252.1IU/mL). Our analysis revealed 136 DEGs distinguishing non-T2 from T2-high asthma. IPA identified predicted inhibition of IgE-FcεRI signaling pathways in non-T2 asthma. Our DEG data showed the expression of IGHV4-39, IGLV1-40, IGLV1-47, IGLV1-44, IGHV1-69, IGLV6-57, IGLV3-19, IGLV3-1, and IGLC7 were downregulated in our non-T2 asthma patient. The non-T2 group exhibited significantly higher concentrations of IL-2, IFN-γ, IL-6, and IL-17A compared to the T2-high group. Our integrated analysis differentiated non-T2 from T2-high asthma by revealing downregulation of specific immunoglobulin genes influencing FcεRI signaling, elevated Th1 cytokines and Th17 cytokines might affect IgE associated sensitization and alter Th2 allergic response.

FREQUENCY OF ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS (ABPA) IN PATIENTS ADMITTED WITH ACUTE EXACERBATION OF ASTHMA IN A TERTIARY CARE HOSPITAL IN KARACHI: A PROSPECTIVE OBSERVATIONAL STUDY

Allergic Bronchopulmonary Aspergillosis (ABPA) is a hypersensitivity reaction to Aspergillus species and often complicates the clinical course of asthma, leading to more severe exacerbations and poor disease control. Despite its clinical relevance, the prevalence of ABPA in asthma patients remains under-reported, especially in developing countries like Pakistan. Objective: This study aimed to determine the prevalence of ABPA among patients admitted with acute exacerbations of asthma at a tertiary care hospital in Karachi, Pakistan. Methods: A prospective observational quantitative study was conducted at the Department of Pulmonary Medicine, Aga Khan Hospital University Karachi, Pakistan from January 2023 to December 2023 in Karachi. The study included 150 isolated patients of either gender, aged between 18 and 80 years, with a clinical diagnosis of asthma or those eligible for spirometry. Data collected included demographic details, past medical history, pulmonary function test results, and serological data for ABPA diagnosis. The presence of ABPA was confirmed by elevated serum total IgE concentration, specific IgE to Aspergillus fumigatus, and radiological findings. Statistical analysis was conducted using SPSS, with p-values < 0.05 considered statistically significant. Results: The study revealed an overall prevalence of ABPA in 20% of the 150 patients with acute asthma exacerbations. Serum total IgE concentration was significantly higher in the ABPA group (450 IU/mL) compared to the non-ABPA group (p < 0.05). Additionally, patients with ABPA had significantly lower FEV1 (60% predicted) compared to those without ABPA (p < 0.05). Conclusion: The study highlights a notable prevalence of ABPA among asthma patients experiencing acute exacerbations. This underscores the importance of raising clinical awareness and implementing timely diagnostic strategies for ABPA in asthma management, which could significantly improve patient outcomes.

Rank correlation between atopic comorbidity and laboratory parameters in allergic rhinitis

One of the current cutting-edge problems in allergy and ENT is the study of comorbidity in allergic rhinitis, which is the most common atopic disease among all other atopies. Two decades ago, a new endotype of the disease, local allergic rhinitis, was discovered. In the past, some patients with typical complaints of chronic nasal congestion, persistent runny nose, and other similar symptoms, did not display such characteristic diagnostic criteria as positive allergy skin tests and an increased value of serum total IgE and specific IgE antibodies. They were qualified by allergists and ENT specialists as individualists with non-allergic rhinitis and, accordingly, did not receive adequate treatment. However, their symptoms remained, prompting them to abuse decongestants and resulting in an increased burden on the cardiovascular system. This, along with the burden of concomitant pathology, including other atopies, can be considered a significant medical and social problem. With the purpose to study rank correlation between comorbidity and three laboratory biomarkers, 46 patients with allergic rhinitis were examined. The list of parameters included two routine items such as serum total IgE and eosinophilic cationic protein, and rarely studied IL-4 in skin exudate. Clinical analysis showed that significantly more often allergic rhinitis in patients was combined with bronchial asthma (in 39.1%, p 0.05), less often with food allergy (in 19.6%), atopic dermatitis (in 10.9%), insect allergy (in 8.7%), and allergic urticaria (in 4.5%). In one case, local perennial rhinitis was identified, accompanied by conventional seasonal rhinitis with a high content of serum total IgE and positive allergic skin tests with pollen allergens. Skin tests with household allergens, including house dust mite products, showed a negative result. This case was regarded as a manifestation of the so-called “double” allergic rhinitis. The Spearman correlation demonstrated a negative mean strength relationship between comorbidity and serum IgE and eosinophilic cationic protein (p 0.05). The seemingly paradoxical result can be interpreted quite logically, taking into account immunopathogenetic mechanisms of allergic inflammation. In particular, with an increase in the frequency of atopic comorbidity, the migration of eosinophils from the blood to sites of eosinophilic inflammation increases.

Phenotypes of occupational bronchial asthma from the standpoint of immunopathogenesis

IIntroduction. Currently, occupational bronchial asthma is considered as a phe notypically and genetically heterogeneous disease. The assessment of clinical data, func tional features, and immunopathogenesis opens up new opportunities in assessing the development, predicting the characteristics of the course, and working out a personalized approach to pharmacotherapy of occupational asthma, as well as in developing an individ ual strategy for its prevention. The purpose of the study was to determine clinical and immunological markers of the risk of developing occupational asthma under conditions of exposure to sensitizing substances in various phenotypes of this disease. Materials and methods. The study included 170 patients with various OA phenotypes and 50 participants in the control group. The pulmonary function test was carried out on the CareFusion MicroLab Desktop Spirometer (Great Britain). The levels of IL-17, TNF-α, vas cular endothelial growth factor (VEGF), MCP-1, IFN-γ, and total IgE in blood serum were determined by solid-phase enzyme immunoassay using kits and reagents (OOO «Protein contour», «Vector-Best», «Diatex-E», «DIA-plus», «Pharmacia diagnostika»). Results. For the first time, the features of clinical and immunological manifestations in allergic and non-allergic OA phenotypes, as well as phenotypes of OA combination with occupational chronic obstructive pulmonary disease and metabolic syndrome were es tablished; the features of formation, immunopathogenesis, and prognosis in various phe notypes of occupational bronchial asthma were revealed. This allows recommending the determination of these immunological parameters during in-depth periodic medical exam inations of workers under conditions of exposure to sensitizing and irritating substances for differential diagnosis of various phenotypes of occupational bronchial asthma in a specialized inpatient examination. Limitations of the study. The study has regional (Samara region) and professional (in terms of detailing the working conditions in the studied comparison groups) limitations. Conclusion. The identified clinical, immunological, and genotypic features in various OA phenotypes and the established profiles of OA genotypes can optimize the approach to early diagnosis, prognosis, prevention, and pharmacotherapy of this disease, as well as expand the list of immunological study indicators used during preliminary and periodic medical examinations, in-depth examination of patients with occupational bronchial asth ma in occupational disease clinics and occupational pathology centers, and the application of new reliable criteria for predicting the course of the disease.

Clinical characteristics and factors associated with mucus plugs under bronchoscopy in children hospitalized for acute asthma attack.

To describe clinical characteristics of hospitalized children with acute asthma attacks complicated with mucus plugs and to investigate the factors associated with mucus plugs in asthma children. This retrospective study analyzed hospitalized children and adolescents with acute asthma attacks from January 2016 to December 2021. The demographic information and characteristics were collected. Subjects were categorized into the mucus plug group and the control group based on the bronchoalveolar lavage results. The Logistic regression analyses were utilized to assess the relative factors associated with mucus plugs. All data were analyzed using SPSS 22.0. This study included 242 individuals. Out of the 151 subjects who underwent bronchoscopy, 62.9% were classified in the mucus plug group and 37.1% in the control group. The subjects with dyspnea had a higher proportion in the mucus plug group (52.6% vs. 26.8%). The serum total IgE level of the mucus plug group was lower than the control group. The proportion of subjects who were diagnosed with asthma for the first time during hospitalization (87.4% vs. 76.8%) and combined with respiratory infection (91.6% vs. 82.1%) in the mucus plug group might be higher than that in the control group. More subjects in the mucus plug group were administered systemic glucocorticoid, magnesium sulfate, aminophylline, and mucolytic drugs after hospitalization. In multivariable analysis, diagnosed with asthma for the first time during hospitalization (OR = 4.404; 1.101-17.614), dyspnea (OR = 4.039; 1.306-12.496), and cesarean (OR = 0.274; 0.092-0.812) might be associated with mucus plug in children hospitalized for an acute asthma attack. While our retrospective study suggests that some clinical features of children hospitalized with asthma who have mucus plugs differ from those without, further studies are required.

B-044 Development and Evaluation of an Assay for the Detection of Human Total IgE in Serum on the Fully Automated Chemiluminescence Immunoassay Platform - Autolumo® 2000 Plus Analyzer

Abstract Background The escalating prevalence of allergic diseases on a global scale, affecting approximately 20% of the world’s population, has become a significant health concern. Clinical determination of total IgE in serum and plasma is used as an aid to the diagnosis of allergic diseases. The tIgE CLIA Microparticles Kit is a chemiluminescent microparticle immunoassay for the quantitative determination of total IgE concentrations in human serum. This kit, integrated with the AutoLumo® 2000 Plus Analyzer, offers an automated, cutting-edge platform for total IgE detection. This streamlined combination provides clinicians with a reliable tool for comprehensive and efficient allergic diseases diagnosis. Methods The performance of tIgE CLIA Microparticles Kit was evaluated on AutoLumo® A2000 Plus automated chemiluminescence analyzer and compared to a well-characterized platform (Elecsys IgE II on Cobas e601, Roche). This assay is based upon the two-step sandwich method. During detection, the patient sample and the anti-IgE coated microparticles solution were added sequentially. Unbound components were washed off after incubation. The formation of a complex occurred with the subsequent addition of a HRP conjugated anti-IgE antibody solution. The catalysis of chemiluminescent substrates by this complex generated a measurable light signal recorded as RLUs (Relative Light Units). A 2-point calibrator was used to analyze the tIgE antibody concentrations in the serum sample. The limit of blank (LoB), limit of detection (LoD), limit of quantitation (LoQ), accuracy, repeatability, linearity, specificity, on-board stability and real-time stability of the assay kit were evaluated. Serum samples (n=220) that had been previously well characterized were used for method comparisons. Results The tIgE CLIA Microparticles assay demonstrated a measurement range of 5-2500 IU/mL, with LoB, LoD, and LoQ values of ≤3 IU/mL, ≤4 IU/mL, and ≤5 IU/mL, respectively. The accuracy of the assay kit was assessed by trueness and precision following CLSI EP15-A2 and EP5-A2 guidelines. The trueness was evaluated using WHO IRP 11/234 as the reference standard, the estimate %bias between the expected and measured mean value was ≤5%. The average %CV of the intra-run and inter-run precision were 5.00% and 3.24% respectively, with a linearity of R≥0.990. The specificity to tIgE is evident, with no cross-reactivity to IgA, IgG, and IgM (≤100 μg/mL), and minimal interference from rheumatoid factor (RF) and anti-nuclear antibodies (ANA) (<10%). Furthermore, based on the CLSI EP7-A2 guideline, it showed no endogenous interference with bilirubin (30 mg/dL), hemoglobin (250 mg/dL), and triglycerides (3000 mg/dL) and no exogenous interferences with 14 commonly used allergy treatment drugs except Omalizumab (360μg/mL). Notably, the assay remains stable on-board for 28 days and exhibits real-time stability for up to 12 months at 2-8ᵒC. Clinical evaluation, involving 220 samples covering the linearity range of 5.0-2500 IU/mL, reveals a strong correlation (R>0.990) and the bias was within 15% when compared to a reference kit according to the CLSI EP9-A2 guideline. Conclusions Autolumo® Analyzers, in conjunction with the tIgE CLIA Microparticles Assay, presents a fully automated chemiluminescence immunoassay platform for accurate and cost-effective screening to aid allergic diseases diagnostics with excellent specificity, precision, and on-board stability.

EQUAL ABPA Score 2024: A Tool to Measure Guideline Adherence for Managing Allergic Bronchopulmonary Aspergillosis.

Allergic bronchopulmonary aspergillosis (ABPA) is a complex lung disease associated with significant morbidity. The ABPA Working Group (AWG) of the International Society for Human and Animal Mycology (ISHAM) revised their management guidelines in 2024, but there is currently no standardised tool to assess adherence to these recommendations. We extracted key recommendations from the updated 2024 ISHAM-AWG guidelines, focusing on critical areas: screening and diagnosis of ABPA, managing acute and treatment-dependent ABPA, and monitoring treatment response. Each item was assigned a score ranging from zero to three. We assigned negative scores to interventions not recommended by the guidelines. We identified 38 items indicative of optimal clinical care for patients with ABPA. The score for screening asthmatics for ABPA was set at three points. For diagnosing ABPA, 16 items were included, with a score ranging from 12 to 16 points, depending on the specific components used (predisposing conditions, serum A. fumigatus-specific IgE and IgG, serum total IgE, blood eosinophil count and chest computed tomography). The management of acute ABPA comprised 11 items, with a maximum score of three points. For treatment-dependent ABPA, there were nine items (scores ranging from -3 to 6). Follow-up care comprised 10 items with a maximum score of 10-13 points, covering imaging, spirometry, testing serum total IgE levels and therapeutic drug monitoring. The EQUAL ABPA score has been developed as a comprehensive tool to quantify guideline adherence. Future studies will evaluate to which extent guideline adherence is associated with improved clinical outcomes for patients with ABPA.

Pinewood VOC emissions protect from oxazolone-induced inflammation and dysbiosis in a mouse model of atopic dermatitis

Pinewood, increasingly used in construction and interior fittings, emits high amounts of volatile organic compounds (VOCs), which tend to accumulate in indoor air. Whether indoor VOCs affect the development of atopic dermatitis (AD) is a matter of debate. We aimed to evaluate the effects of pinewood VOCs on the development of AD-like inflammatory phenotype and linked microbiome alterations, both hallmarks of AD. An oxazolone-induced mouse model of AD was exposed to three different VOC concentrations emitted by pinewood plates throughout the experiment. The disease course and associated immunological and microbiological changes were evaluated. To validate and translate our results to humans, human keratinocytes were exposed to a synthetic pinewood VOCs mixture in an AD environment. Pinewood emitted mainly terpenes, which at a total concentration of 5 mg/m3 significantly improved oxazolone-induced key AD parameters, such as serum total IgE, transepidermal water loss, barrier gene alteration, inflammation, and dysbiosis. Notably, exposure to pinewood VOCs restored the loss of microbial richness and inhibit Staphylococci expansion characteristic of the oxazolone-induced mouse AD model. Most beneficial effects of pinewood VOCs were dose-dependent. In fact, lower (<3 mg/m3) or higher (>10 mg/m3) pinewood VOC levels maintained only limited beneficial effects, such as preserving the microbiome richness or impeding Staphylococci expansion, respectively. In the human in-vitro model, exposure of keratinocytes grown in an AD environment to a pinewood VOCs mixture reduced the release of inflammatory markers. In conclusion, our results indicate that airborne phytochemicals emitted from pinewood have beneficial effects on an AD-like phenotype and associated dysbiosis. These investigations highlight the effects of terpenes as environmental compounds in the prevention and/or control of atopic skin disease.

A real-world data analysis of distribution and inconsistency between total serum IgE and allergen-specific IgE results in clinical practice.

The inconsistency between serum total IgE (tIgE) and allergen-specific IgE (sIgE) results is often encountered in clinical practice, but the distribution and influencing factors of the inconsistent results have not been fully understood. The aim of this study was to analyze the distribution and inconsistency between tIgE and sIgE test results. A retrospective study, from the electronic medical records of 2139 patients who underwent both tIgE and sIgE tests, from January to December 2023 was reviewed. The tIgE and sIgE results and their distribution, as well as their inconsistency, were analyzed based on sex, age, and disease subgroups. 36.2% of the patients had a positive sIgE, and 43.7% had an elevated tIgE level. sIgE and tIgE results were discordant in nearly 30% of patients, with no difference between genders, while individuals aged over 60 exhibited a significantly higher inconsistency rate than the other age groups, and the inconsistency rate between tIgE and sIgE results was significantly different among different tIgE levels, sIgE grades, positive allergen count and positive allergen types. In addition, patients with chronic urticaria (CU) had a higher inconsistency rate than those with other allergic diseases, but the difference was not statistically significant. The overall inconsistency rate between tIgE and sIgE results was about 30%. The elderly group older than 60 years old is more likely to have inconsistent results, and tIgE level, sIgE level, the number and type of positive allergens also affected the consistency of tIgE and sIgE results.

Prognostic value of serum total IgE and FeNO levels in children with atopic constitution bronchiolitis

Bronchiolitis is a significant factor contributing to bronchial asthma in infants and young children. After treatment, recurrent wheezing symptoms often occur, especially in children with atopic constitution, who tend to have more severe conditions and poorer prognosis. Therefore, exploring the prognostic value of total serum immunoglobulin E (tIgE) and fractional exhaled nitric oxide (FeNO) levels in children with atopic constitution who suffer from bronchiolitis is of great significance. A total of 260 children with bronchiolitis admitted to our hospital from October 2020 to June 2022 were regarded as the research subjects with prospective study, according to whether the children had atopic constitution, they were grouped into non atopic constitution group (n = 156) and atopic constitution group (n = 104); after 6 months of treatment, children with atopic constitution were grouped into a good prognosis group (n = 58) and a poor prognosis group (n = 46) based on their prognosis; in addition, 260 healthy children who underwent physical examination and had clinical data consistent with those of children with bronchiolitis were regarded as the reference group. The serum tIgE and FeNO levels of each group were compared; multivariate Logistic regression was applied to analyze the prognostic factors of children with atopic constitution bronchiolitis; ROC curve was applied to analyze the predictive value of tIgE and FeNO levels after treatment for the prognosis of children with atopic constitution bronchiolitis. The tIgE levels in the control group, non-atopic group, and atopic group [(123.54 ± 29.62) IU/mL, (245.71 ± 30.59) IU/mL, (316.46 ± 31.78) IU/mL, respectively] increased sequentially, with statistically significant differences (F = 1766.954, P = 0.000). The FeNO levels in the control group, non-atopic group, and atopic group [(8.36 ± 3.57) ppb, (15.28 ± 3.69) ppb, (19.84 ± 3.58) ppb, respectively] also increased sequentially, with statistically significant differences (F = 765.622, P = 0.000). The tIgE, FeNO, proportion of patients with asthma family history, and proportion of patients with allergic family history in the poor prognosis group were obviously higher than those in the good prognosis group (P < 0.05). Multivariate Logistic regression analysis showed that family history of asthma, family history of allergies, tIgE, and FeNO were influencing factors for the prognosis of children with atopic bronchiolitis (P < 0.05). The AUC of the combination of tIgE and FeNO in predicting the prognosis of children with atopic constitutional bronchiolitis was 0.910, with a sensitivity of 78.26% and a specificity of 93.10%, which was superior to the independent prediction of tIgE and FeNO (Zcombined detection−tIgE = 2.442, Zcombined detection−FeNO = 3.080, P = 0.015, 0.002). The levels of tIgE and FeNO in children with atopic constitution bronchiolitis are obviously increased, and the combination of the two has high predictive value for the prognosis of atopic constitution bronchiolitis.

Reduction of circulating IgE and allergens by a pH-sensitive antibody with enhanced FcγRIIb binding

Allergen-crosslinked IgE triggers allergy by interacting with its receptor on basophils and mast cells. The anti-IgE monoclonal antibody omalizumab can alleviate allergy by competing with the receptor for IgE binding. However, along with neutralization, omalizumab also inhibits IgE degradation, which is clinically associated with high dose and total IgE accumulation problems. In this study, we have developed an IgE-eliminating antibody on the basis of omalizumab, which has pH-dependent Fabs and an Fc with high affinity for FcγRIIb. In mice, the antibody rapidly eliminated total serum IgE to baseline levels and caused lower free IgE levels than omalizumab. At low dosages, the antibody also exhibited favorable IgE elimination effects. In addition, the antibody can degrade the corresponding allergen with the removal of IgE, addressing the allergy from its source. Introduction of the M252Y/S254T/T256E (YTE) mutation into this antibody prolongs its serum half-life without reducing potency. Thus, this engineered antibody holds a promising therapeutic option for allergy patients. Mechanistic insights are also included in this study.

Anti-Allergic and Anti-Inflammatory Effects of Lidocaine-Derived Organic Compounds in a House Dust Mite-Induced Allergic Rhinitis Mouse Model.

Allergic rhinitis (AR) is a common chronic disease that significantly impacts the quality of life. Lidocaine is known to have anti-inflammatory and immunomodulatory effects. This study evaluated the effect of lidocaine analogs in a Dermatophagoides pteronyssinus (DP)-induced AR mouse model. An AR model was developed using BALB/c mice via intraperitoneal sensitization with DP and intranasal challenge with DP. One hour before stimulation with DP, lidocaine analogs, EI137 and EI341 (at a dose of 0.5 or 5 ug/g), were administered intranasally. Nasal symptoms and serum total IgE, interleukin (IL)-4, IL-10, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α levels were evaluated. Reverse-transcription polymerase chain reaction was used to determine IL-4, IL-10, and IFN-γ, as well as the expression of their mRNA transcription factors in the sinonasal mucosa. Histologic changes were evaluated using hematoxylin and eosin and periodic acid-Schiff staining. The DP-induced AR mouse model had increased serum levels of total IgE and cytokines. EI137 and EI341 significantly suppressed the levels of total IgE, IL-4, and TNF-α. Intranasal instillation of EI137 and EI341 significantly inhibited IL-4, IL-10, and IFN-γ mRNA expression, as well as inflammatory cells and mucus-producing goblet cells. Lidocaine analogs also suppressed DP-stimulated IL-4, IFN-γ, and IFN-γ production by splenocytes. Intranasal instillation of EI137 and EI341 exhibited anti-allergic and anti-inflammatory effects, influenced by Th1 and Th2 inflammatory cytokines. These lidocaine analogs suppressed DP-induced sinonasal mucosal inflammation, inflammatory cell infiltration, and mucus hypersecretion.

Intermittent ozone inhalation during house dust mite-induced sensitization primes for adverse asthma phenotype

The ability of air pollution to induce acute exacerbation of asthma is well documented. However, the ability of ozone (O3), the most reactive gaseous component of air pollution, to function as a modulator during sensitization is not well established. C57BL/6 J male mice were intranasally sensitized to house dust mite (HDM) (40 μg/kg) for 3 weeks on alternate days in parallel with once-a-week O3 exposure (1 ppm). Mice were euthanized 24 h following the last HDM challenge. Lung lavage, histology, lung function (both forced oscillation and forced expiration-based), immune cell profiling, inflammation (pulmonary and systemic), and immunoglobulin production were assessed. Compared to HDM alone, HDM + O3 leads to a significant increase in peribronchial inflammation (p < 0.01), perivascular inflammation (p < 0.001) and methacholine-provoked large airway hyperreactivity (p < 0.05). Serum total IgG and IgE and HDM-specific IgG1 were 3–5 times greater in HDM + O3 co-exposure compared to PBS and O3-exposed groups. An increase in activated/mature lung total and monocyte-derived dendritic cells (p < 0.05) as well as T-activated, and T memory lymphocyte subset numbers (p < 0.05) were noted in the HDM + O3 group compared to HDM alone group. Concurrent O3 inhalation and HDM sensitization also caused significantly greater (p < 0.05) lung tissue interleukin-17 pathway gene expression and mediator levels in the serum. Redox imbalance was manifested by impaired lung antioxidant defense and increased oxidants. O3 inhalation during allergic sensitization coalesces in generating a significantly worse TH17 asthmatic phenotype.

The function and mechanism of Human nasal mucosa-derived mesenchymal stem cells in allergic rhinitis in mice.

To investigate the immunomodulatory effects and potential mechanisms of human nasal mucosa-derived mesenchymal stem cells(hNMSCs) on mouse allergic rhinitis, and to compare them with human umbilical cord-derived mesenchymal stem cells (hUCMSCs). hNMSCs and hUCMSCs were isolated and cultured for identification from human nasal mucosa and umbilical cord tissues. A co-culture system of LPS-stimulated RAW264.7 cells/mouse peritoneal macrophages and MSCs was employed.Changes in inflammatory factors in RAW264.7 cells and the culture medium as well as the expression of NF-κB signaling pathway in RAW264.7 cells were detected. Forty-eight BALB/c mice were randomly divided into control, OVA, hNMSCs, and hUCMSCs groups. An allergic rhinitis (AR) model was established through ovalbumin (OVA) stimulation and treated with hNMSCs and hUCMSCs. Subsequent assessments included related symptoms, biological changes, and the expression of the NF-κB signaling pathway in the nasal mucosa of mice. MSCs can be successfully isolated from human nasal mucosa. Both hNMSCs and hUCMSCs interventions significantly reverseed the inflammation induced by LPS and suppressed the upregulation of the NF-κB signaling pathway in RAW264.7 cells. Treatment with hNMSCs and hUCMSCs alleviated mouse allergic symptoms, reduced levels of total IgE, OVA-specific IgE and IgG1 in mouse serum, TH2-type cytokines and chemokines in mouse nasal mucosa, and TH2-type cytokines in mouse spleen culture medium, while also inhibiting the expression of the NF-κB signaling pathway in the nasal mucosa of mice. moreover, the hNMSCs group showed a more significant reduction in OVA-specific IgG1 in serum and IL-4 expression levels in mouse spleen culture medium compared to the hUCMSCs group. Our findings suggest that hNMSCs can ameliorate allergic rhinitis in mice, with a certain advantage in anti-inflammatory effects compared to hUCMSCs. The NF-κB pathway is likely involved in the anti-inflammatory regulation process by hNMSCs.Therefore, hNMSCs might represent a novel therapeutic approach for allergic rhinitis.

Dupilumab as Therapeutic Option in Polysensitized Atopic Dermatitis Patients Suffering from Food Allergy.

IgE-mediated food allergy is characterized immunologically by a type 1 immune response triggered upon exposure to specific foods and clinically by a broad range of manifestations and variable severity. Our understanding of food allergy within the allergic march of atopic dermatitis (AD) is still incomplete despite the related risk of unpredictable and potentially severe associated reactions such as anaphylactic shock. The aim of this pilot study was to investigate the effects of dupilumab, an IL-4/IL-13 monoclonal antibody approved for AD, on the allergic sensitization profile of patients with AD and type 1 hypersensitivity-related comorbidities, including oral allergy syndrome, anaphylaxis, and gastrointestinal disorders. We conducted an observational pilot study with a longitudinal prospective design, enrolling 20 patients eligible for treatment with dupilumab. Laboratory exams for total serum IgE, specific IgE, and molecular allergen components were performed at baseline and after 16 weeks of therapy. Our results demonstrate a statistically significant decrease in molecular components, specific IgE for trophoallergens, and specific IgE for aeroallergens following treatment with dupilumab. We suggest that modulating type 2 immunity may decrease IgE-mediated responses assessed with laboratory exams and therefore could minimize allergic symptoms in polysensitized patients. Upcoming results of randomized controlled trials investigating dupilumab in food allergy are highly anticipated to confirm its potential effect in the treatment of IgE-mediated food allergies.

Biochemical and nutrients profile of asthma patients with perceived food allergy in India- a hospital based case control study

Objective: The current study explored the biochemical and dietary profile of asthma patients with and without perceived food allergy (FA). Methods: A case-controlled study was conducted with 286 patients (143 asthmatics with perceived food allergy and 143 age, sex, SES matched asthmatics with no perceived food allergy) aged 15-40 years. The blood sample was collected, and Food Frequency Questionnaire was recorded for laboratory investigations and nutrients calculation respectively. Relevant biochemical parameters (complete blood picture, total serum IgE etc.) were analyzed in the blood samples and macro and micronutrients (calories, protein, fat, Vit-B complex, Calcium etc.) were calculated and comparisons were made between the cases and controls. Results: Most of the cases had higher BMI (27.5±4.82) than controls (23.3±4.51) (p≤0.05); 59(41.3%) and 46(32.2%) had BMI in the range of 25-30 and &gt;30. The perceived food allergy in asthmatics was associated with biochemical parameters (Hb, TLC, Eosinophil counts, Monocytes, Serum IgE, Serum protein and serum calcium) and nutrients[protein(42.24±7.63g/d), fat(23.86±4.70g/d), thiamine(0.77±0.15mg/d), riboflavin(1.20±0.19mg/d), pyridoxine(1.53±0.16mg/d), folic acid(70.80±8.69µg/d), cobalamine(0.70±0.03 mg/d), ascorbicacid(34.51±4.26mg/d), calcium(304.10±62.36 mg/d), and iron(17.94±4.97 mg/d)] as compared to their counterparts with no perceived food allergy(p≤0.05). Conclusion: Asthmatics eliminate food items based on self-perception which may lead to nutrients deficiency and abnormal blood reports. There is a need to confirm FA diagnosis and develop appropriate framework to manage FA in asthmatics. More studies are needed to estimate association of asthma and food allergy with micronutrient deficiency and Body Mass Index. Key words: asthma, food allergy, laboratory investigations, nutrients intake, body mass index

The impact of adverse reactions on adherence to sublingual immunotherapy for Japanese cedar pollinosis and house dust mite allergy in Japan

Background Allergen immunotherapy is the only treatment that can achieve remission for allergic diseases. Aims/Objectives To investigate the three-year adherence to sublingual immunotherapy for Japanese cedar pollinosis and house dust mite allergy at a clinic in Japan and identify factors that influence adherence and severe adverse reactions. Material and Methods In total, 174 patients aged 12 years or older who started sublingual immunotherapy for Japanese cedar pollinosis (n = 72), house dust mite allergy (n = 55), or both (n = 47) between May 2017 and June 2018. Patient age, sex, type of pharmacotherapy used, adverse reactions, blood test results, and duration of continuous treatment were investigated. Results The three-year treatment continuation rate was 40.8%. Adverse reaction rates were 12.6% for cedar pollinosis and 40.2% for house dust mite allergy. Patients with dose reductions due to severe reactions had lower first-year continuation rates. In the MITICURE® group, patients with severe reactions had significantly higher serum total IgE levels. Severe reactions were more common in MITICURE® patients with seven or more positive antigen types. Conclusions and Significance Severe adverse reactions reduced early adherence.