Total IgE Research Articles

Childhood allergy and anxiety/depression in early adulthood: A longitudinal study in the ALSPAC birth cohort.

Allergic disease and common mental disorders frequently co-occur. However, little is known about the longitudinal impact of childhood allergy on the subsequent risk of developing anxiety or depression, and the possible biological mechanisms for this. We performed longitudinal analyses of data from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. The baseline sample comprised n=5256 children with allergy data available at age 7yrs. We used multivariable regression to test associations between childhood allergy at age 7yrs and: a) four inflammatory markers at age 9yrs; b) depression and anxiety measures between ages 10-24yrs. Allergy measures included biological markers (total serum immunoglobulin E (tIgE), number of positive skin prick tests (SPTs)), and presence of eczema, asthma and/or food allergy (mother reported). Inflammatory markers were interleukin-6 (IL-6), C-reactive protein (CRP), IL-4 and IL-13. We used structural equation modelling to test whether inflammatory markers mediated the association between tIgE and depression/anxiety. tIgE and having≥1 positive SPT at age 7 were associated with IL-6 levels at age 9 (adjusted β=0.09; 95% CI 0.06-0.13; p<0.001 and adjusted β=0.06; 95% CI 0.03-0.09; p<0.001 respectively), but not with CRP, IL-4 or IL13 levels. We found no strong evidence of an association between childhood allergy and subsequent depression/anxiety during adolescence and early adulthood. This finding was consistent across biological and mother-reported allergy measures. Biological markers of childhood allergy are associated with IL-6, a key inflammatory cytokine. However, childhood allergy may not have a large long-term effect on subsequent depression/anxiety.

Association of LPCAT1-rs8352 genetic variant with susceptibility and severity of pediatric bronchial asthma: a case-control study

BackgroundThis study aimed to investigate the possible association of LPCAT1-rs8352 genetic variant (single nucleotide change C to G) with the onset and severity of pediatric asthma. Additionally, the study examined the influence of LPCAT1-rs8352 genotypes on asthma-related biomarkers including blood eosinophils count (BEC), eosinophil cationic protein (ECP), high-sensitivity C-reactive protein (hs-CRP), and immunoglobulin E (IgE) and on lung function [forced expiratory volume in one second (FEV1) and the forced vital capacity (FVC)].Patients and methodsThe study included ninety-six participant grouped into two groups: G1 (46 asthmatics) and G2 (50 healthy controls). ECP, hs-CRP, and total IgE serum levels were measured using their corresponding ELISA kits. Neonatal blood DNA was extracted using the Gene JET™ Whole Blood Genomic DNA Purification Mini Kit. Genotyping was performed by RT-PCR.ResultsA significantly higher proportion of individuals in G1 had the LPCAT1-rs8352 CC and GC genotypes compared to G2 (p < 0.001). Individuals with the CC genotype exhibited significantly more severe asthma, along with elevated levels of BEC, ECP, hs-CRP, and total IgE. Those with the GC genotype demonstrated a similar, though less severe, pattern, followed by individuals with the GG genotype. The FEV1 and FVC values showed the opposite trend, with individuals having the GG genotype exhibiting the highest lung function values.ConclusionThe LPCAT1-rs8352 allele C is associated with pediatric asthma onset and severity. Further research on the LPCAT1 genetic variants may provide a deeper understanding of pediatric bronchial asthma mechanisms and lead to improved management strategies.

Effectiveness of Tralokinumab in Different Phenotypes of Atopic Dermatitis: A Real-World Study.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by pruritus and a relapsing course, affecting approximately 25% of children and 4-7% of adults. This study evaluated the efficacy, safety, and quality-of-life impact of tralokinumab, a humanized monoclonal antibody targeting interleukin-13 (IL-13), in treating moderate-to-severe AD in a real-world setting, with a focus on different AD phenotypes. An observational cohort of 30 adults treated with tralokinumab for ≥ 16weeks was analyzed. Clinical and demographic data were collected, and outcomes were assessed using the Eczema Area and Severity Index (EASI), Dermatology Life Quality Index (DLQI), and numeric rating scales (NRS) for pruritus and sleep disturbances. By week16, 60% achieved a 75% improvement inEASI (EASI75)and 31% reached a 90% improvement inEASI (EASI90), reflecting substantial clinical improvements. A ≥ 4-point reduction in pruritus NRS was observed in 63% of patients by week16, increasing to 70% by week32. Similarly, 75% achieved significant improvements in sleep disturbance NRS by week16, with sustained effects through week32. Subgroup analysis revealed superior clinical responses in patients with early-onset AD and atopic comorbidities. Lower total immunoglobulinE (IgE) levels at week16 correlated with better outcomes, suggesting total IgE as a potential biomarker. By week32, 70% of patients had a DLQI ≤ 5, indicating minimal quality-of-life impact. Additionally, 88% reached at least one therapeutic target, and 81% met composite endpoints combining clinician-assessed and patient-reported outcomes. The safety profile was consistent with clinical trials, with mild conjunctivitis and injection site reactions as the most common adverse events. These findings support tralokinumab as an effective and well-tolerated treatment, emphasizing the importance of phenotype-specific approaches in AD management.

Changes in Gut Microbiota According to Disease Severity in a Lupus Mouse Model

Systemic lupus erythematosus (SLE) is a multifaceted autoimmune disease driven by immune dysregulation. This study investigated the relationship between gut microbiota and lupus severity using the MRL/lpr lupus mouse model. Mice were grouped based on total immunoglobulin (Ig)G, IgG2a levels, and urine albumin-to-creatinine ratio (ACR), allowing for the comparison of gut microbiota profiles across different disease severities. Interestingly, severe lupus mice exhibited significant reductions in Ruminiclostridium cellulolyticum, Lactobacillus johnsonii, and Kineothrix alysoides, while Clostridium saudiense, Pseudoflavonifractor phocaeensis, and Intestinimonas butyriciproducens were enriched. These microbial shifts correlated with elevated IgG, IgG2a, and ACR levels, indicating that changes in the gut microbiome may directly influence key immunological markers associated with lupus severity. The depletion of beneficial species and the enrichment of potentially pathogenic bacteria appear to contribute to immune activation and disease progression. This study suggests that gut microbiota dysbiosis plays a critical role in exacerbating lupus by modulating immune responses, reinforcing the link between microbial composition and lupus pathogenesis. Our findings provide the first evidence identifying these distinct gut microbial species as potential contributors to lupus severity, highlighting their role as key factors in disease progression.

Efficacy and Safety of Dupilumab Across Different Th2-Type-Mediated Diseases: A Real-Life Preliminary Experience

Background: Dupilumab, a fully human monoclonal antibody targeting the interleukin (IL)-4/IL-13 pathway, is able to dampen T helper (Th)2-mediated inflammation in several conditions characterized by this particular type of phlogosis. The aim of this study was to review the efficacy and safety of dupilumab treatment in conditions underpinned by Th2-type inflammation in a cohort of real-world patients referred to our outpatient clinic. Methods: Data from all patients with atopic dermatitis, chronic rhinosinusitis with nasal polyps, asthma, and other Th2-type-mediated inflammatory conditions treated with dupilumab were retrospectively reviewed. Results: Twenty-two patients were included in the study: 14 with atopic dermatitis, 5 with chronic rhinosinusitis with nasal polyps, 2 with asthma, and 1 with prurigo nodularis; some of the patients had more than one atopic condition. A complete response was observed in 13 out of 22 patients (59.1%); when partial responses were included in the analysis, the overall response rate was 86.4%. No adverse events were recorded, either locally or systemically. Total IgE levels dropped in all patients, in some cases reaching values close to those typically observed in nonatopic subjects. When eosinophilia was present at baseline, this also normalized during dupilumab treatment. Conclusions: Dupilumab was safe and effective across multiple conditions driven by Th2-type chronic inflammation; effective interference with the Th2-type pathway was inferred by the progressive reduction in serum total IgE levels, which reached the normal range in a fraction of patients, and by the reduction in peripheral blood eosinophil counts. Further studies in different Th2-mediated diseases are warranted.

Antibodies and Inflammation: Fecal Biomarkers of Gut Health in Domestic Ruminants.

Gastrointestinal infections present major challenges to ruminant livestock systems, and gut health is a key constraint on fitness, welfare, and productivity. Fecal biomarkers present opportunities to monitor animal health without using invasive methods, and with greater resolution compared to observational metrics. Here we developed enzyme-linked immunosorbent assays for three potential fecal biomarkers of gut health in domestic ruminants: two immunological (total immunoglobulin [Ig]A and total IgG) and one inflammatory (lactoferrin). We analytically validated the assays, then evaluated whether they could be used as a biomarker of clinically diagnosed gastrointestinal pathologies in cattle (Bos taurus), and finally comparedthem with helminth fecal egg counts in sheep (Ovis aries). The analytes were detected above the lower limits of detection in cattle, sheep, and goats. Fecal IgA and lactoferrin were higher in cattle with infectious pathologies (strongyles, coccidiosis and symptomatic Johne's disease) compared to healthy controls. Lactoferrin was additionally higher in animals with infectious pathologies compared to noninfectious pathologies, and to asymptomatic Johne's cases. No significant relationships were found with sheep fecal egg counts. These initial findings suggest that fecal IgA and lactoferrin may be useful biomarkers of poor gastrointestinal health in cattle, and that fecal lactoferrin is specific to active inflammation caused by infectious agents. These could be incorporated into the growing suite of noninvasive ecoimmunological tools and used to understand ruminant gut health in a range of species. Applications include improving treatment regimens for gastrointestinal infections, and understanding wildlife physiological responses to infectious challenges.

Integrating immunity, antioxidative status, and gene regulation against nickel and high-temperature stress in fish: selenium nanoparticles for mitigation.

Fish face health hazards due to high-temperature (T) stress and the toxicity associated with nickel (Ni), both of which can occur in aquatic ecosystems. The accumulation of nickel in fish may pose risks to human health when contaminated fish are consumed. Consequently, the goal of this study was to clarify how selenium nanoparticles (Se-NPs) help Pangasianodon hypophthalmus by reducing the effects of nickel and high-temperature stress. The fish were reared under different experimental conditions as follows: a control group (no exposure to Ni and T, and fed a control diet); a group concurrently exposed to Ni and T while fed a control diet; and groups concurrently exposed to Ni and T while being fed supplemented diets with Se-NPs at 0.5mgkg-1 and 1.0mgkg-1 for 38days. The growth performance of fish exposed to nickel and high-temperature (Ni + T) stress was significantly improved by supplementation with selenium nanoparticles (Se-NPs) at 0.5mgkg-1. This supplementation also upregulated the expression of growth hormone (GH) and growth hormone receptor (GHR1) genes, while considerably downregulating the myostatin (MYST) gene. Fish subjected to Ni + T stress exhibited markedly elevated cortisol levels, which were notably reduced by Se-NPs at 0.5mgkg-1. Moreover, Se-NPs at 0.5mgkg-1 significantly downregulated the expression of stress-related genes, including Caspase 3a (Cas 3a), CYP450, iNOS, and HSP70. Fish fed Se-NPs supplemented diet and exposed to Ni + T stress demonstrated enhanced levels of TNFα and total immunoglobulins, indicating an improved immune response. Dietary Se-NPs also led to a significant reduction in oxidative stress markers, such as glutathione-S-transferase, catalase, and superoxide dismutase, in stressed fish. While Ni + T stress reduced acetylcholine esterase activity, dietary Se-NPs restored these activities. Furthermore, the inclusion of Se-NPs in the diet markedly enhanced the detoxification of nickel in various fish tissues. In conclusion, the study demonstrates that dietary supplementation with Se-NPs at 0.5mgkg-1 effectively mitigates the adverse effects of Ni + T stress in fish by modulating gene expression, alleviating cellular metabolic stress, and enhancing physiological functions.

Inhaled corticosteroids in asthma and chronic obstructive pulmonary disease combined phenotype: when to use and what to expect?

The term "asthma-chronic obstructive pulmonary disease (COPD) combined phenotype" describes patients with persistent airflow limitation and features of both asthma and COPD. There is a lack of data on effective treatments for this group, often excluded from asthma or COPD trials. Inhaled corticosteroids (ICS) are standard for asthma, while bronchodilators are key for COPD. This study is a prospective interventional study that included 43 patients diagnosed with the asthma-COPD overlap phenotype, as per Sin et al. criteria, who were treated as COPD priorly and followed over one year. These patients received additional treatment with a moderate-dose ICS metered dose inhaler beclamethasone 800 mcg daily, in addition to their optimal inhaled bronchodilator therapy. Follow-up spirometry along with reversibility, fractional exhaled nitric oxide (FeNO), blood investigations like total eosinophil count (TEC) and immunoglobulin E (IgE) were done; sputum eosinophils were measured, and a history of exacerbations was noted. These parameters were compared with baseline values obtained prior to the initiation of ICS to evaluate the impact of the intervention. Among the 43 individuals in the study population, the majority fell within the age group of 60-69 years. The addition of ICS to bronchodilators over a one-year period resulted in significant improvements in their forced expiratory volume in one second. Additionally, there was a notable reduction in the FeNO level, along with decreases in the TEC, serum IgE levels, and sputum eosinophils. Although the number of exacerbations decreased during the study period in this subgroup, this reduction did not reach statistical significance. Based on these findings, the study suggests that ICS should be considered as an adjunct to inhaled bronchodilators for the management of stable COPD patients exhibiting features of the asthma-COPD combined phenotype.

Inula japonica Thunb. and its active compounds ameliorate airway inflammation by suppressing JAK-STAT signaling.

Asthma, a chronic inflammatory disease, remains a global health challenge due to its complex pathophysiology and the limited treatment efficacy. This study explored the effect of Inula japonica Thunb. water extract (IJW) on asthma and its protective mechanisms. To assess the effects of IJW, we established an experimental asthma model in BALB/c mice using ovalbumin (OVA). Airway hyper-responsiveness (AHR) in response to methacholine was measured. We quantified inflammatory cell infiltration and cytokine and chemokine levels in bronchoalveolar lavage fluid (BALF), as well as total IgE levels in serum. Staining with hematoxylin and eosin and periodic acid-Schiff was used to examine the impact of IJW on lung pathology. We performed RNA sequencing to identify differentially expressed genes, which were subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. We used interleukin (IL)-4/IL-13-treated human bronchial epithelial (HBE) cells to explore the associated mechanisms. IJW showed therapeutic effects against OVA-induced asthma by alleviating AHR, peribronchial inflammation, mucus hypersecretion, and collagen fiber deposition. It reduced total IgE levels in the serum and IL-4, IL-5, IL-13, eotaxin, macrophage-derived chemokines, and periostin levels in BALF. In IL-4/IL-13-treated HBE cells, IJW and its components suppressed the Janus kinase-signal transducer and activator of the transcription (JAK-STAT) signaling. These findings support IJW's potential as a pharmacological agent for allergic airway inflammation and asthma.

Immunoglobulin E, the potential accelerator of comorbid psoriasis and atherosclerosis.

Immunoglobulin (Ig) E is a key mediator in the induction and maintenance of allergic inflammation, characterized by a Th2-dominated immune response. Recently epidemiological studies have showed that elevated serum total IgE levels or an increased abundance of mast cells (MCs) at the lesion site are observed in psoriatic patients with cardiovascular diseases (CVD), such as atherosclerosis. Although the underlying mechanisms by which IgE synergizing with MCs in promoting these chronic immune-inflammatory diseases remain unclear, the interleukin (IL)-23/IL-17 axis appears to play a crucial role in comorbidity of psoriasis and atherosclerosis. High IgE production may result from IL-17A response, further exacerbating inflammatory pathways involved in both psoriasis and atherosclerosis. This review explores the possible mechanisms of IgE in these comorbid conditions, reinforcing the rationale for IL-17A targeted biologics in the treatment of psoriasis andatherosclerosis comorbidity. Additionally, IgE is proposed as a potential therapeutic target for alleviating patients suffering from these comorbidity conditions.

Proinflammatory cytokine genes and their polymorphic variants: clinical and laboratory profiles in the Federal Firefighting Service employees of the EMERCOM of Russia

Relevance. Genetic determinants of multifactorial diseases are critical for assessing the risk of genetic diseases and their prevention, especially among the workforce exposed to industry-related dangerous and aggressive occupational factors. Firefighters perform combat service duties in extremely unfavorable industrial environments associated with occupational diseases. Respiratory diseases are among the pathologies with highest incidence rates in firefighters. In addition to environmental factors, the development of these diseases (especially bronchial asthma and chronic obstructive pulmonary disease) is largely driven by impaired immune system – one of the three critical regulatory systems involved in pathogenetic mechanisms of various diseases, including inflammatory diseases. Polymorphic gene variants of inflammatory mediators – in particular cytokine genes and their receptors – mediate the immune system activity and can impact its functionality, susceptibility, or resistance to disease development.The objective is to analyze how interleukin 1β, 4, 6, 13, TNF and interleukin 6 receptor genes, as well as their polymorphic variants are associated with respiratory diseases and changes in the biomarker profiles showing immune response intensity in the employees of the Federal Firefighting Service of the EMERCOM of Russia. Methodology. Molecular genetic profiling and immunology tests were performed in 70 employees of the Federal Firefighting Service of the EMERCOM of Russia to analyze proinflammatory cytokine genes and their polymorphic variants. Real-timePCR was used to analyze the interleukin 1β, 4, 6, 13, TNF and interleukin-6 receptor genes and their polymorphic variants. Immunological examination evaluated the blood monocyte subpopulations and relative count of type 2 T-helper cells; flowcytometry and immunochemiluminescence assays were used to evaluate immune response biomarkers in peripheral blood and total immunoglobulin E (IgE) respectively.Results and discussion. The analysis provides evidence that minor alleles of most polymorphic cytokine genes are associated with a proinflammatory phenotype, which is especially apparent for genotypes comprising several minor alleles. Allele A at rs1 800 629 polymorphic TNF gene exposed a direct correlation with respiratory diseases, as well as with increased monocyte differentiation. Allele T of IL4 rs2243250 gene and allele A of IL1β rs16944 gene were associated with increased proinflammatory monocyte count. Elevated count of type 2 T-helper mediators of humoral response, especially of allergicorigin, was observed in individuals with C/C IL6 rs1 800 795 and G/G IL1β rs16944 genotype.Conclusion. The obtained results suggest that evaluation of cytokine gene polymorphic variants is a promising strategy to predict the risk of respiratory diseases in firefighters. Prompt assessment of genetic predisposition to a proinflammatory phenotype paves the way towards prevention and early detection of inflammatory diseases in this cohort of workers.

Monitoring M-Protein, Therapeutic Antibodies, and Polyclonal Antibodies in a Multiparametric Mass Spectrometry Assay Provides Insight into Therapy Response Kinetics in Patients with Multiple Myeloma.

Background/Objectives: Multiple Myeloma (MM) is a hematologic malignancy caused by clonally expanded plasma cells that produce a monoclonal immunoglobulin (M-protein), a personalized biomarker. Recently, we developed an ultra-sensitive mass spectrometry method to quantify minimal residual disease (MS-MRD) by targeting unique M-protein peptides. Therapeutic antibodies (t-Abs), key in MM treatment, often lead to deep and long-lasting responses. However, t-Abs can significantly decrease the total polyclonal immunoglobulin (Ig) levels which require supplemental IgG infusion. Here, we demonstrate the simultaneous monitoring of M-proteins, t-Abs, and polyclonal Ig-titers using an untargeted mass spectrometry assay, offering a comprehensive view of therapy response. Methods: Sera collected between 2013 and 2024 from four patients and cerebrospinal fluid (CSF) from one patient who received various t-Abs were analyzed with MS-MRD. M-protein sequences were obtained with a multi-enzyme de novo protein sequencing approach. Unique peptides for M-proteins and t-Abs were selected based on linearity, sensitivity, and slope coefficient in serial dilutions. Ig constant regions were monitored using isotype-specific peptides. Results: The MS-MRD multiplex analysis provided detailed information on drug concentrations and therapy response kinetics. For example, in two patients with refractory disease over five lines of therapy, the MS-MRD analysis showed that the deepest responses were achieved with bispecific t-Ab (teclistamab) treatment. M-protein and t-Ab were also detectable in the CSF of one patient with MS-MRD. Conclusions: This proof-of-concept study shows that the multiplex monitoring of the M-protein, any t-Ab combination, and all Ig-isotypes within one mass spectrometry run is feasible and provides unique insight into therapy response kinetics.

DNA methylation at birth and IgE trajectories from birth to adolescence, different patterns between White and Asian.

We aim to assess association of DNA methylation (DNAm) at birth with total immunoglobulin E (IgE) trajectories from birth to late adolescence and whether such association is ethnicity-specific. We examined the association of total IgE trajectories from birth to late adolescence with DNAm at birth in two independent birth cohorts, the Isle of wight birth cohort (IOWBC) in UK (n = 796; White) and the maternal and infant cohort study (MICS) in Taiwan (n = 60; Asian). Biological pathways and methylation quantitative trait loci (methQTL) for associated Cytosine-phosphate-Guanine sites were studied. Two total IgE trajectories, high vs. low, were inferred from each of the two cohorts. Associations of DNAm at 103 CpGs with IgE trajectories in IOWBC and at 476 CpGs in MICS were identified. Between the two cohorts, of the identified CpGs, one was in common, methQTL site cg16711274 (mapped to gene MINAR1), and 17 pathways were common with at least four linked to airway diseases. The findings suggest at-birth epigenetics may explain ethnicity differences in total IgE trajectories later in life.

Efficacy of different probiotic regimens for allergic rhinitis: A network meta-analysis.

To evaluate the efficacy of different probiotic species in the treatment of Allergic rhinitis (AR), we used network meta-analysis (NMA), which provides a foundation for evidence-based therapeutic selection. Nine databases were searched from their inception until April 30, 2024. Stata 17.0 and Review Manager 5.4 were used to conduct the NMA. The main outcomes included total nasal symptom score (TNSS), Rhinitis Quality of Life (RQLQ) global scores, total and specific IgE levels, blood eosinophil count, efficacy rate, and adverse events. 31 randomized controlled trials (RCTs) were included, involving 2544 patients with AR. In the NMA, in terms of reducing TNSS: Saccharomyces>Mix>Bifidobacterium>Enterococcus faecalis>Lactobacillus>Bacillus>conventional therapy; in terms of reducing RQLQ: Mix>Lactobacillus>Enterococcus faecalis>conventional therapy; in terms of reducing Total IgE: Mix>Bifidobacterium>Lactobacillus>Tetragenococcus halophilus>conventional therapy; in terms of reducing Special IgE: Mix>conventional therapy>Bifidobacterium>Lactobacillus>Leuconostoc; in terms of reducing blood eosinophil count: Lactobacillus>conventional therapy>Mix; in terms of improving the efficacy rate: Saccharomyces>Mix>conventional therapy. No serious adverse events were reported regarding safety. Probiotic mixtures may be the most effective in reducing RQLQ, Total IgE, and Special IgE; Saccharomyces may be the most efficacious in reducing TNSS and improving the efficacy rate; and Lactobacillus may be the most effective in reducing blood eosinophil count. Overall, probiotic mixtures demonstrated better combined efficacy.

Replacement of fishmeal with Quinoa Husk (Chenopodium quinoa) for mitigating multiple stresses in Pangasianodon Hypophthalmus

The fishmeal is boon for aquaculture production in this recent pollution and climate change era. However, the demand of fishmeal is enhancing in many folds which needs to find alternative to fishmeal in cheap price. The present investigation addresses these issues with quinoa husk (QH). An experiment was performed to evaluate replacement of fishmeal by QH in different proportionate at 0, 15, 20, 25, 30 and 35%. The study was designed with 12 treatments as control, stressors group (concurrent exposed to ammonia, arsenic and high temperature stress, NH3+As+T), group fed with QH at 15, 20, 25, 30 and 35% without and with stressors (NH3+As+T) in Pangasianodon hypophthalmus for 105 days. The optimization of QH dose for growth performance such as food conversion ratio, growth rate, protein efficiency ratio and specific growth rate with respect to protein percentage and obtained 26%. The oxidative enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione-s-transferase (GST) and glutathione peroxidase (GPx) in gill, kidney and liver tissues were significantly lowered by replacement of fishmeal by QH at 25% in fish reared under arsenic and ammonia toxicity and high temperature stress (NH3+As+T). The neurotransmitter enzyme (AChE) in brain tissue was noticeably enhanced by QH at 25%. The aspartate amino transferase (AST) and alanine amino transferase (ALT) as well as malate dehydrogenase (MDH) and lactate dehydrogenase (LDH) in gill and liver were significantly reduced by QH at 25% in fish reread under multiple stresses (NH3+As+T). The nitro blue tetrazolium (NBT), blood glucose, albumin, globulin, total protein, A:G ratio, myeloperoxidase (MPO) and total immunoglobulin (Ig) were noticeably improved by supplementation of QH at 25–30% in fish reared under NH3+As+T. The amylase, protease and lipase were significant improved with replacement of fishmeal by QH at 25%. The histo-pathological alterations were marked in liver and gill tissues, whereas these tissues were protected by QH at 25% in fish reared under control and stress condition (NH3+As+T). The present study revealed that replacement of fishmeal at 25% by QH could be a better replacement for improvement in anti-oxidative status, acetylcholine esterase and growth performance in fish reread under NH3+As+T stress.

The Significance of Fractional Exhaled Nitric Oxide, Fractional Nasal Exhaled Nitric Oxide and Lung Function Tests in Children with Moderate-to-Severe Allergic Rhinitis.

Fractional nasal exhaled NO (FnNO), fractional exhaled NO (FeNO) and lung function tests were performed in children with moderate-to-severe persistent allergic rhinitis (AR) to investigate the significance of the above indices in the assessment and diagnosis of children with AR. A total of 135 children with persistent AR were selected and divided into moderate-to-severe and mild groups; serum total immunoglobulin E (IgE), peripheral blood eosinophil counts (EOS), FnNO, FeNO, and lung function tests were performed. Children in the moderate-to-severe group had increased levels of FnNO and FeNO and decreased levels of forced expiratory flow at 75% of forced vital capacity as a percentage of the predicted value (FEF75%) and maximum mid-term expiratory flow as a percentage of the predicted value (MMEF%) . IgE in children with AR was positively correlated with FeNO and FnNO and negatively correlated with FEF75% . EOS was positively correlated with FnNO. FeNO was negatively correlated with FEF75% and forced expiratory flow at 50% of forced vital capacity as a percentage of the predicted value (FEF50%). FnNO was negatively correlated with FEF75%, FEF50%, and MMEF%. FnNO, FeNO, and pulmonary function tests may help assess disease severity and level of disease control in children with persistent AR.

Prevalence and features of allergic bronchopulmonary aspergillosis, United States, 2016-2022.

The epidemiology of allergic bronchopulmonary aspergillosis (ABPA) in the United States is not well-described. To estimate national ABPA prevalence among patients with asthma or cystic fibrosis, characterize ABPA testing practices, and describe ABPA clinical features, treatment, and 6-month outcomes. We used the 2016-2022 Merative™ MarketScan® Commercial/Medicare and Multi-State Medicaid Databases to identify cohorts of patients with 1) asthma, 2) cystic fibrosis (CF), and 3) ABPA. We calculated ABPA prevalence per 10,000 patients with asthma or CF, assessed diagnostic testing for ABPA among patients with severe asthma, and described features of patients with ABPA using diagnosis and procedure codes. The overall ABPA prevalence among patients with asthma was 2.8/10,000 (Commercial/Medicare) and 1.0/10,000 (Medicaid). ABPA prevalence increased with asthma severity (Commercial/Medicare: mild 1.3, moderate 9.3, severe 70.6, Medicaid: mild 0.3, moderate 2.4, severe 32.4). Among patients with CF, ABPA prevalence was 183.7/10,000 (Commercial/Medicare) and 134.6/10,000 (Medicaid). Among patients with severe asthma, 10.3% (Commercial/Medicare) and 7.4% (Medicaid) received total immunoglobulin E testing, which is recommended for ABPA diagnosis. Among all patients with ABPA (Commercial/Medicare: n = 1,564, Medicaid: n = 410), ABPA treatments included inhaled corticosteroids (>70%), systemic corticosteroids (>62%), and antifungals (>18%). Patients with ABPA and Medicaid were more likely to experience hospitalization (45.1% vs. 22.5% of patients with Commercial/Medicare insurance) and respiratory failure (18.5% vs. 10.9%). This analysis provides initial estimates of national ABPA prevalence. Further studies could identify potential barriers to ABPA testing and investigate potential factors affecting payer-related differences in ABPA burden.

Relationship between serum ECP and TIgE levels and the risk of postoperative recurrence in patients with chronic rhinosinusitis with nasal polyps.

This study was undertaken to assess the association between the likelihood of surgical recurrence and serum ECP and TIgE levels in chronic rhinosinusitis with nasal polyps (CRSwNP). Clinical information was gathered retrospectively from 166 cases of surgically treated CRSwNP as well as 60 cases of chronic rhinosinusitis without nasal polyps (CRSsNP). A comparative analysis on serum levels of total immunoglobulin E (TIgE) and eosinophil cationic protein (ECP) was carried out between the two groups. The CRSwNP patients were assigned into recurrence and non-recurrence groups based on the absence/presence of disease recurrence after a 2-year follow-up. An analysis was conducted on the correlation between the patients' clinical data and their serum ECP and TIgE levels. Receiver operating characteristic (ROC) curves were utilized to assess the clinical utility of these two biomarkers. The CRSwNP participants had higher serum levels of ECP and TIgE (4.28 ± 0.81 > 3.58 ± 0.77 ng/L, P < 0.001; 52.99 ± 8.62 > 15.65 ± 3.25 KU/L, P < 0.001) compared to CRSsNP participants. Univariate analysis indicated that neutrophil ratio, lymphocyte ratio, Lund-Kennedy score, Lund-Mackay score, SNOT-22 score, olfactory function score, and postoperative recurrence were significantly correlated with serum ECP and TIgE levels. Higher serum levels of TIgE and ECP (4.89 ± 0.79 < 4.11 ± 0.72, P < 0.001; 58.74 ± 8.27 < 51.40 ± 8.04, P < 0.001) were detected in the recurrence groups vs. the non-recurrence group. Multivariate analysis showed that serum ECP and TIgE were independent risk factors for recurrence of CRSwNP. Serum ECP and TIgE levels were found to be predictive of postoperative recurrence risk in CRSwNP patients (AUC: 0.77, 0.74, 0.84; P < 0.05) according to ROC curve analysis. Significant differences were not observed in any general clinical data. The findings suggest that elevated serum ECP and TIgE levels in patients with CRSwNP can be as good predictors for the risk of recurrence after endoscopic sinus surgery.

Evaluation of Intestinal Permeability Using Serum Biomarkers in Learning Early About Peanut Allergy Trial.

Intestinal barrier dysfunction may lead to a break in tolerance and development of food allergy (FA). There is contradictory evidence on whether intestinal permeability (IP) is altered in IgE-mediated FA. Thus, we sought to determine whether IP differed between children with eczema who did (FA group) or did not (atopic controls, ACs) develop FA and whether peanut sensitization, allergy, and early introduction impacted IP using serum biomarkers zonulin, soluble CD14, and Intestinal Fatty Acid Binding Protein among randomly selected participants enrolled in the Learning Early About Peanut allergy trial. FA group was defined as having at least one FA at either baseline (4-11 months) or 60 months of age (V60). ACs had eczema at baseline and no FA at either visit. Serum IP markers (sIPMs) were measured by ELISA at baseline and V60, and their relationship with the clinical characteristics of participants was analyzed using parametric tests and linear regression models. We evaluated 237 FA subjects and 76 ACs. sIPM levels were similar in FA subjects and ACs at baseline and V60. Age when the child first developed any FA (< 1 year vs. > 1 year), eczema severity, peanut sensitization, peanut allergy, and early peanut introduction were not statistically significantly associated with sIPM levels. Total IgE and eosinophil levels, peanut-specific IgE, IgG4, and IgG4/IgE ratio were not correlated with sIPM levels. No differences in sIPMs were detected to support altered IP in infants with FA compared to ACs or following early peanut introduction among peanut-sensitized children.

First-in-human study on tolerability, pharmacokinetics and pharmacodynamics of single and multiple escalating doses of XKH001, a recombinant humanized monoclonal antibody against IL-25 in healthy Chinese volunteers

Background: XKH001 is a recombinant humanized IgG1 monoclonal antibody against IL-25 for the treatment of type 2 inflammatory diseases. This study aimed to evaluate the tolerability, pharmacokinetics, and pharmacodynamics of XKH001 in humans for the first time. Research design and methods: This clinical investigation adopted a randomized, double-blind, and placebo-controlled single ascending dose (SAD) and multiple ascending dose (MAD) design. Results: XKH001 was well tolerated in healthy Chinese subjects. Following repeated administration, XKH001 showed a slow absorption with a median Tmax of 4–7 days and a mean half-life (t1/2) of 22–25 days. The accumulation ratio ranged from 1.34 to 1.99. The exposure was mostly dose proportional, with a mean slope of 0.85–1.06. All subjects tested negative for ADA (except three subjects tested positive). The subjects who received 600 mg XKH001 in the MAD study showed a 78.2 ng/mL decrease in the total immunoglobulin E (IgE) level 85 days after the first administration, while the subjects who received matched placebo exhibited only a 8.6 ng/mL decrease.Conclusions: XKH001 showed favorable safety and pharmacokinetics profiles and a low immunogenicity in its first-in-human study. The data support its further clinical evaluation in patients with type 2 inflammatory diseases.