Serum IgE Levels Research Articles

EPID-32. ELEVATED SERUM IGE IS LINKED TO IMPROVED GLIOBLASTOMA SURVIVAL, PARTICULARLY AMONG FEMALES

Abstract Prior epidemiological research shows a correlation between serum immunoglobulin E (IgE) levels and decreased risk of glioma. However, the relationship between IgE and the prognosis of glioma remains poorly understood. This study seeks to investigate how factors such as sex, tumor subtype, and IgE class influence the association of serum IgE levels with both glioma risk and survival outcomes. METHODS- In this investigation, we conducted a case-control study utilizing participants enrolled in the UCSF Adult Glioma Study from 1997 to 2010. We measured serum IgE levels for total, respiratory, and food allergy in adults diagnosed with glioma (n=1,696), and controls (n=1,135) matched based on age, sex, and race/ethnicity. Logistic regression, adjusted for patient demographics, was employed to evaluate the correlation between IgE levels and glioma risk. Multivariable Cox regression, adjusted for patient-specific and tumor-specific factors, was utilized to compare survival outcomes between the elevated and normal IgE groups. RESULTS- Increased levels of total IgE were linked to a decreased risk of both IDH wildtype (OR=0.65, 95% CI: 0.54-0.78) and IDH mutant glioma (OR=0.65, 95% CI: 0.50-0.85). In multivariable Cox regression analysis, heightened respiratory IgE levels were associated with enhanced survival among individuals with IDH wildtype glioma (HR=0.78, 95% CI: 0.67-0.91). Notably, this improved survival was more pronounced in females (HR=0.71, 95% CI: 0.53-0.96) compared to males (HR=0.80, 95% CI: 0.66-0.97), resulting in median survival improvements of 6.2 months (P<.001) and 1.6 months (P=0.003), respectively. CONCLUSION- Increased levels of serum IgE were associated with reduced risk of glioma overall, and improved prognosis for IDH wildtype glioma, which was particularly strong in females. These findings hint at potential sexual dimorphism in the antitumor activity of IgE-mediated immune responses, suggest an important role for IgE assessment in glioblastoma clinical trial design, and provide justification for investigations into IgE-based therapeutics.

Can We Better Understand, Diagnose, and Treat Ketamine‐Induced Uropathy, and Can It Be Reversed? ICI‐RS 2024

ABSTRACTIntroductionKetamine, a versatile anesthetic, has seen increased recreational use, leading to significant health issues, including ketamine‐induced uropathy (KIU). KIU manifests with lower urinary tract symptoms (LUTS) and can involve the upper urinary tract. This study aims to provide a comprehensive overview of KIU, addressing its pathophysiology, diagnostic strategies, and treatment options; and to define/identify future research priorities.MethodsDuring the 2024 meeting of the International Consultation on Incontinence Research Society (ICI‐RS) in Bristol, a dedicated Proposal (P) convened to explore KIU. This initiative involved a thorough review of existing literature, expert presentations, and consensus‐driven discussions. The methodology ensured a comprehensive exploration of KIU from both clinical and pre‐clinical perspectives, leading to actionable research recommendations.ResultsUnderstanding the mechanisms of KIU is crucial for developing effective treatment options targeting specific pathophysiological pathways. Key findings include bladder fibrosis driven by transforming growth factor‐β1 (TGF‐β1), elevated purinergic responses and upregulated P2X1 purinoceptor expression, decreased barrier function due to increased expression of antiproliferative factor (APF), and functional loss of the bladder through Cav1.2 channel blockade. Research indicates that fibrosis, typically considered irreversible, may be mitigated. However, the exact timing and extent of fibrosis initiation and its impact on long‐term outcomes require further research. LUTS typically improve after ketamine cessation but relapse upon resumption, indicating a hypersensitivity mechanism involving elevated serum IgE levels. Advanced stages of KIU do not always correlate with LUTS severity, shedding light on potential systemic effects and the need for evaluating liver enzymes. Furthermore, psychological dependency on ketamine, due to its positive perceptive and mood‐altering effects, complicates cessation efforts. Long‐term management requires a holistic approach, integrating medical treatments and supportive measures to help patients navigate life with potentially irreversible complications.ConclusionThis comprehensive review spans from fundamental pathology to practical clinical management, addressing both urological and systemic complications, and bridging insights from animal models to human applications. Developing effective treatment strategies necessitates addressing both the physical and psychological aspects of ketamine dependency.

Effects of different doses of rituximab on immunoglobulin levels in high-risk pediatrics with Burkitt's lymphoma.

Studies have confirmed that rituximab (RTX) can improve the efficacy of BL, but there is a certain effect on the level of immunoglobulin, which will lead to the verification of infection, and the previous study of our center has confirmed that reducing the dose of RTX (4 doses) can achieve a similar effect to the standard dose of RTX (6 doses), can it reduce the effect on the level of immunoglobulin? To date, few studies have concentrated on the effects of immunoglobulin (Ig) on Chinese paediatric patients. This study aimed to examine whether there is a variation in the impact of different doses of RTX on immunoglobulin levels in the high-risk group of children with BL. Clinical data of high-risk pediatric patients with BL who were treated in Beijing Children's Hospital (Beijing, China) were retrospectively analysed. Baseline characteristics and serum Ig levels were collected at four distinct time points (t0 = pre-chemotherapy, t1 = at the end of chemotherapy, t2 = 6 months post-chemotherapy, t3 = 12 months post-chemotherapy). Ig levels were measured at various time points before and after treatment within three RTX treatment groups: R0 group (standard chemotherapy without RTX), R6 group (6 doses of RTX + chemotherapy), and R4 group (4 doses of RTX + chemotherapy). The objective was to compare whether differences existed among the three groups. The results revealed that the study enrolled 300 high-risk BL patients, including 256 boys and 44 girls, distributed across three groups based on RTX dosage: R0 group (n = 38), R6 group (n = 87), and R4 group (n = 175). Median Ig levels were assessed at four time points (t0, t1, t2, t3) for each group. In the R0 group, IgA and IgM levels significantly decreased at t1 compared with t0 (P = 0.006 and 0.002, respectively), while were gradually recovered at t2, returning to t0 levels at t3 (P = 0.073 and 0.293, respectively). IgG levels exhibited no significant difference between t0 and t1 (P = 0.89), reaching their lowest levels at t2 and returning to t0 levels at t3 (P = 0.14). In the R4 group, the minimum levels of IgA, IgM, and IgG were identified at t1 (P < 0.001, < 0.001, and < 0.001, respectively), which were gradually recovered at t2, while remained lower than t0 levels at t3 (P < 0.001, < 0.001, and = 0.005, respectively). The R6 group exhibited reduction in IgA and IgM levels at t1, with gradual recovery at t2 and t3, while remained lower than t0 levels (P = 0.003 and < 0.001, respectively). IgG levels in the R6 group decreased at t1 (P < 0.001) and did not return to t0 levels at t3 (P = 0.004). In the R4 and R6 groups, it was observed that children with hypogammaglobulinemia pre-RTX were more likely to combine with persistent hypogammaglobulinemia (PH-Ig) post-RTX. A 1:1 matched comparison between R4 and R6 groups (78 patients each) revealed consistently higher IgA, IgM, and IgG levels in the R4 group at each time point after chemotherapy. Notably, IgA and IgG levels recovered earlier in the R4 group than those in the R6 group (P < 0.05). Burkitt lymphoma in the high-risk group were more likely to complicated hypoimmunoglobulinemia after treatment, it is important to monitor Ig levels before and during treatment, and to inform replacement therapy for Ig. Compared with standard chemotherapy group, the RTX group had a longer time of low Ig and a slower recovery, reducing the dosage of rituximab can improve the recovery of IgA and IgG levels.

The Influence of Skin Microbial Ecology on γδ T Cell Immune Pathways in Allergic Dermatitis Models in Mice.

Atopic dermatitis (AD) is a complex disease influenced by alterations in the skin microbiome and immune dysregulation. Despite the recognized role of these factors, the specific pathways by which distinct microbial populations affect skin immunity remain insufficiently understood. On a molecular level, the pathogenesis of AD involves critical cytokines such as IL-4, IL-17, interferon-γ (IFN-γ), and IL-10, which contribute to the imbalance in T helper (Th) cell responses. Importantly, gamma-delta (γδ) T cells, which produce these cytokines and infiltrate affected epithelial cells in AD, have been underexplored. This study seeks to alleviate AD symptoms in mice by adjusting both peripheral and local immune environments through the transplantation of skin microbiota. By employing 16S rRNA sequencing, we characterized the skin microbiome of the mouse model. Our results demonstrate that microbiota intervention significantly reduces skin thickening and serum IgE levels in DNFB-induced AD mice. Additionally, changes in skin microbiota modulated immune cell dynamics, restoring the Th1/Th2 balance and leading to clinical improvement. These findings highlight the critical role of skin microbiota in shaping immune responses, positioning microbiota-based therapies as a potential treatment for AD.

Neutrophil-activating protein in Bacillus spores inhibits casein allergy via TLR2 signaling

BackgroundMilk allergy commonly occurs in children, mainly caused by bovine-derived casein (CAS) protein. Neutrophil-activating protein (NAP) of Helicobacter pylori plays an immunomodulatory role with potential to suppress Th2-type immune responses. Bacillus subtilis (B. subtilis) spores are commonly used as oral vectors for drug delivery.ObjectiveTo investigate whether recombinantly expressed NAP on B. subtilis spores could be an effective treatment for CAS allergy in mouse.MethodsAfter CAS sensitization, mice were orally administered B. subtilis spores expressing recombinant NAP for 6 weeks. Allergic symptoms and parameters were evaluated after CAS challenge oral gavage, including allergic inflammation, splenic cytokines, and serum-specific antibodies. Protein levels of Toll-like receptor 2 (TLR2) and c-JUN in the jejunum tissue were measured by western blot. Bone marrow-derived macrophages (BMDMs) were stimulated with inactivated NAP spores to measure the influence on cytokine profiles in vitro.ResultsNAP recombinant spore treatment significantly reduced allergic symptoms and intestinal inflammation. Interleukin-12 and interferon-gamma levels increased, whereas serum CAS-specific IgG1 and IgE levels decreased. TLR2 and c-JUN expression levels were elevated in the jejunal tissue. Inactivated NAP spores polarized BMDMs to the M1 phenotype and enhanced cytokine expression, which were inhibited by a TLR2 neutralizing antibody.ConclusionNAP offers a new strategy in the treatment of CAS allergy by inhibiting the Th2 response, while eliciting macrophages to promote Th1 immune responses.

The Association of Nasal and Blood Eosinophils with Serum IgE Level in Allergic Rhinitis and Asthma: A Case-Control Study.

Allergic rhinitis and asthma are two common respiratory diseases with allergic etiology in the world's population. Eosinophils and serum IgE levels have been known as inflammatory allergy markers for many years. This study aimed to evaluate the correlation of nasal and blood eosinophils with serum IgE levels in allergic rhinitis and asthma patients. This prospective study was done on patients (n = 78) diagnosed with asthma (n = 20), allergic rhinitis (n = 49), and chronic rhinosinusitis with nasal polyposis (CRSwNP) (n = 9) at our hospital in Ahvaz City, Iran. The age of participants in our study ranged from 3 to 73 years, and all of them were subjected to a complete blood count (CBC) test, nasal smear, and determination of serum IgE levels after their consent. There was no correlation between serum IgE level and nasal eosinophil count (p = 0.728) or between serum IgE level and blood eosinophil count (p = 0.657); however, a positive correlation was detected between blood and nasal eosinophil levels (p = 0.003). There is no significant relationship between serum IgE level and eosinophil count in the blood and nasal secretions. Serum IgE level and blood or nasal eosinophil count are both useful biomarkers for monitoring allergic rhinitis and asthma individually, but no diagnostic conclusion can be drawn from their correlation.

The essential oils from Asarum sieboldii Miq. alleviate allergic rhinitis by regulating tight junction and inflammation; Network analysis and preclinical validation

Ethnopharmacological relevanceEssential oils from herbs, including those from Asarum sieboldii Miq., are readily absorbed through mucous membranes, explaining their widespread use in inhalation formulations. Asarum sieboldii Miq. has a long history of traditional use for various medicinal purposes, attributed to its anti-inflammatory, antiallergic, and antioxidant properties. Despite research on Asarum sieboldii Miq. for allergic inflammation in respiratory diseases, detailed mechanistic studies are still lacking. Aim of the studyWe utilized bioinformatics and network pharmacology to identify the effectiveness of Asarum sieboldii Miq. in treating allergic rhinitis (AR). Our aim is to elucidate the potential therapeutic effects of essential oil derived from Asarum sieboldii Miq. (ASO), which is recognized for its diverse pharmacological properties, on AR. Materials and methodsCommon genes associated with the active compounds of ASO and AR were utilized to construct a related network and predict their mode of action. AR was induced in BALB/c mice by exposing them to ovalbumin (OVA) and particulate matter 10 (PM10; airborne particles <10 μm). With induction, aerosolized ASO (0.0002% and 0.02%) were administered via nebulizer for 5 minutes per day, three times a week for 7 weeks. Mice were examined for histopathological changes in the nasal tissue, nasal epithelial inflammation, the production of allergen-specific cytokine response in vitro and in vivo. ResultsThe common genes of ASO and AR were predicted to include 'Tight junction', 'Apoptosis', and 'TGF-beta signaling', which are the main pathways of pathogenesis in AR. Consistent with network prediction, nebulized ASO treatment effectively improved the expression of tight junction-related factors, zonula occludens-1, claudin-1, occludin and junction adhesion molecule A, in OVA+PM10 induced mice. Additionally, it reduced hyperplasia of nasal epithelial thickness, goblet cell counts, and inflammatory cell infiltration (eosinophils, neutrophils, macrophages, and lymphocytes) in nasal lavage fluid, while also alleviating allergic symptoms such as sneezing, rubbing, and serum IgE level when compared to the AR-induced group. The levels of mRNA and protein expression related to tight junctions were restored to normal levels by ASO, as confirmed in immunofluorescence analysis in nasal epithelial cells RPMI2650. Furthermore, treatment of ASO on PM10-treated nasal epithelial cells significantly reduced ROS production, recovered mitochondria membrane potential, and inhibition of the production of proinflammatory cytokines (TNF-α, IL-4, and IL-13) and inflammatory mediators linked to the MAPK/NF-κB signaling pathways. ConclusionIntranasal nebulization of ASO improves TJs and alleviates allergic nasal inflammation in AR. It supports the potential pharmaceutical application of ASO treatment for AR.

Job’s syndrom. Case reports

Primary immunodeficiencies with impaired humoral link are genetically determined diseases characterized by impaired antibody formation. The article presents information about an orphan disease – hyperimmunoglobulinemia E syndrome (hyper-IgE), or Job’s syndrome, which is characterized by elevated IgE levels in the blood serum, recurrent infections and various clinical manifestations (specific abnormalities of connective tissue, skeleton, tooth enamel, neurological disorders, etc.). Historical aspects of Job’s syndrome are described, the importance of immunoglobulins E in the human immune system is shown. It is noted that genetic testing, including sequencing of the STAT3 and DOCK8 genes, plays a decisive role in confirming the diagnosis. Low prevalence of Job’s syndrome is the reason for late diagnosis. Clinical cases of Job’s syndrome, a variant of primary immunodeficiency confirmed genetically, are presented.

Dupilumab use in patients with hypereosinophilic syndromes: a multicenter case series and review of the literature

BackgroundHypereosinophilic syndromes (HES) are defined as hypereosinophilia with eosinophil-related clinical manifestations, some of which overlap in presentation with asthma, atopic dermatitis, eosinophilic esophagitis, and/or chronic rhinosinusitis with nasal polyps (CRSwNP). Dupilumab is approved to treat these conditions but can induce a transient rise in the absolute eosinophil count (AEC) and rare eosinophil-related complications. ObjectiveTo determine whether eosinophil-related complications of dupilumab are increased in HES. MethodsRetrospective chart review of patients with HES treated with dupilumab enrolled on an IRB-approved research protocol at the National Institutes of Health (NCT00001406) or receiving care at Walter Reed National Military Medical Center. Clinical response and treatment-emergent adverse events were recorded. Serum mediators were assessed in a subset of patients before and after dupilumab using stored samples. ResultsAmong the 28 patients (15 male, 13 female; median age 41.5), the most common prescribing indication for dupilumab was CRSwNP (n=11). Twenty-three patients (82%) showed significant clinical improvement on dupilumab. Hypereosinophilia (AEC >1.5x109/L) recurred or worsened in 9/20 patients on dupilumab monotherapy. Moreover, 4/20 (20%) patients developed an eosinophil-related complication with dupilumab discontinuation and/or addition of eosinophil-lowering therapy. None of the 8 patients who received dupilumab while in hematologic remission on an eosinophil-lowering biologic developed hypereosinophilia or an eosinophil-related complication. Serum IgE and eotaxin levels decreased on dupilumab therapy. ConclusionThese data suggest that dupilumab is effective in treating residual symptoms in HES patients but that the incidence of eosinophil-related complications is increased. Concomitant eosinophil-lowering therapy may reduce the risk of eosinophil-related complications during dupilumab therapy in patients with HES.

Assessing humoral immunity in daily practice: A retrospective study in a pediatric tertiary center

The evaluation of humoral immunity is usually performed through the assessment of serum immunoglobulin levels, vaccine titer responses, and B-cell enumeration and phenotyping. We performed a retrospective study assessing humoral immunity in 469 pediatric patients referred at the Sainte-Justine University Hospital Center. Almost half of the patients had at least one abnormal humoral immunological parameter at their evaluation, with low vaccine response titer to protein antigen being the most frequent. Fifteen patients (3.2 %) had a proven monogenic IEI, and 21 patients (4.5 %) required Ig replacement. Besides the infectious burden, hypoIgG remains the only parameter associated with Ig replacement therapy after the age of 6 years. Low antibody titers against conjugate vaccines had low sensitivity and positive predictive values for starting Ig replacement. Our study highlights the challenge of evaluating the humoral function in the pediatric population with suspected IEI with significant age and sex-dependent variability between parameters.

GPR55 antagonist CID16020046 suppresses DNCB-induced atopic dermatitis-like symptoms by suppressing Th1/Th2/Th17 populations in mice

G protein-coupled receptor 55 (GPR55) is a lipid-sensing receptor that plays a role as an immune mediator and is primarily upregulated during immune cell activation. There is a lack of knowledge about the role of GPR55 in allergic inflammatory diseases such as atopic dermatitis. The purpose of this study was to investigate the role of GPR55 through the use of its antagonist, CID16020046, in an atopic dermatitis mouse model. It was found that BALB/c mice develop lesions similar to those associated with atopic dermatitis following sensitization and repeated exposure to 1-chloro-2,4-dinitrobenzene (DNCB). It was found that CID16020046 (1 mg/kg, i. p.) alleviated the atopic dermatitis-like symptoms as well as immune dysregulation caused by DNCB. Based on histopathological analysis, CID16020046 reduced ear thickening and mast cell counts in the dermis. CID16020046 decreased DNCB-induced increases in serum IgE levels, as measured using enzyme-linked immunosorbent assays. A significant reduction in lymph node hypertrophy was also observed with CID16020046 as well as significant reductions in CD4+ T helper 1 (Th1), Th2, and Th17 cells in the lymph nodes. As a result of the administration of CID16020046, cytokines of Th1 (IFN-γ), Th2 (IL-4 and IL-13), and Th17 (IL-17 A) types were also reduced in the skin and lymph nodes. In conclusion, blocking GPR55 alleviates DNCB-induced atopic dermatitis-like symptoms, suggesting that GPR55 is a potential therapeutic target for allergic inflammatory diseases via immunoregulation.

Hydrogen Gas Inhalation Alleviates Airway Inflammation and Oxidative Stress on Ovalbumin-Induced Asthmatic BALB/c Mouse Model

Airway inflammatory diseases, such as asthma, are a global public health concern owing to their chronic inflammatory effects on the respiratory mucosa. Molecular hydrogen (H2) has recently been recognized for its antioxidant and anti-inflammatory properties. In this study, we examined the therapeutic potential of H2 in airway inflammation using an ovalbumin (OVA)-induced BALB/c mouse model of allergic asthma. Female BALB/c mice were sensitized and challenged with OVA to induce airway inflammation, and 30 mice were randomly divided into five groups: NT (non-treatment), HTC (3% H2 treatment only), NC (negative control, OVA only), PC (positive control, OVA + intranasal 1 mg/mL salbutamol 50 μL), and HT (H2 treatment, OVA + inhaled 3% H2). Various inflammatory and oxidative stress (OS)-induced markers such as white blood cells (WBCs) and their differential counts, lung histology, cytokine levels such as interleukin (IL)-4, (IL)-5, (IL)-13, interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), granulocyte-macrophage colony-stimulating factor (GM-CSF), (IL)-10, reactive oxygen species (ROS), nitric oxide (NO), glutathione peroxidase (GPx), and catalase (CAT), and total immunoglobulin E (IgE) levels were investigated. Our results showed that inhaled H2 significantly reduced inflammatory cell infiltration, OS markers, and pro-inflammatory cytokine expression while upregulating antioxidant enzyme activity. Furthermore, H2 also significantly decreased serum IgE levels, a marker of allergic inflammation. Collectively, our findings suggest that H2 inhalation is a promising treatment option for airway inflammation, offering a novel approach with potential clinical applications.

Diagnostic value of serum thymus and activation-regulated chemokine (TARC) in fatal asthma

ObjectivesAsthma, a chronic inflammatory airway disease, is characterized by airway hyperresponsiveness and structural changes. Accurate postmortem diagnosis is crucial because of legal and insurance implications, necessitating differentiation from other causes of sudden death. Thymus and activation-regulated chemokine (TARC) is a chemokine that potentially acts as a biomarker of asthma. This study evaluated the diagnostic value of serum TARC combined with immunoglobulin E (IgE) levels as biomarkers in forensic settings. ResultsThe subjects were 100 autopsy cases, categorized into fatal asthma (n = 25), acute myocardial infarction (AMI) (n = 37), and traumatic deaths (n = 38). TARC levels were significantly elevated in asthma (525.68 ± 801.87 pg/mL) compared with AMI (180.35 ± 109.37 pg/mL) and trauma (173.26 ± 105.01 pg/mL) cases. Similarly, serum IgE levels were higher in asthma (3363.72 ± 7023.46 KU/L) than in AMI (130.92 ± 260.79 KU/L) and trauma (134.53 ± 195.41 KU/L) cases. ROC curve analysis showed that serum TARC had a sensitivity of 68.0 % and specificity of 73.6 % (AUC 0.763, cut-off value of 225 pg/mL). In comparison, serum IgE had a sensitivity of 80 % and specificity of 86.1 % (AUC 0.881, cut-off value of 307 KU/L). The combined use of TARC and IgE increased the diagnostic specificity to 95.8 %. ConclusionsSerum TARC and IgE are valuable biomarkers for diagnosing fatal asthma in forensic settings. While serum TARC levels correlate with Th2-mediated inflammation, the combined measurement of TARC and IgE enhances the diagnostic accuracy, providing significant specificity for confirming asthma diagnosis.

A Multi-centre Analysis of Serum IgE Levels in Atopic Dermatitis

Abstract Objective: To assess the characteristics of total immunoglobulin E (IgE) and allergen-specific IgE (sIgE) to 20 common allergens in 154 patients with atopic dermatitis (AD). To assess the correlation of clinical food allergy with positive food allergens’ sIgE results. We further discuss the significance of IgE as a potential biomarker for AD disease severity. Methods: A total of 154 AD patients were collected from 15 hospitals nationwide in China from 2019 to 2021. Serum IgE was measured using reverse-enzyme immuno capture test (REAST). Patients were required to have at least one positive sIgE (N ≥ 0.35 IU/mL). Patients were divided into groups according to gender, age, disease severity, and region. SPSS 26.0 software was used for statistical analysis. Results: Compared with adolescent and adult, AD in infancy and childhood showed significantly higher frequencies of positive sIgE to food allergens, including egg, cow milk, and wheat (P &lt; 0.01). However, adolescent and adult AD showed significantly higher frequencies of positive sIgE to inhaled allergens, dermatophagoides farinae, and house dust mite. In addition, sIgE in different sexes were different. Compared with women, men showed higher frequencies of positive allergen-specific IgE level to wheat, dermatophagoides farinae, and house dust mite. The most common food allergens with elevated sIgE levels were egg (71%), cow milk (39%) and wheat (32%). However, AD patients reported seafood, including crab, shrimp, and fish, as the most frequent food allergens which aggravate their disease in their daily life. Only 18 (12%) patients reported definite correlation of clinical practice with positive food allergens’ IgE results. Among 154 sIgE-positive patients, 99 patients had an increase of total IgE (≥60 IU/ml). TotalIgE (tIgE) levels were significantly different between mild (193 ± 239 IU/mL), moderate (170 ± 202 IU/mL), and severe (375 ± 343 IU/mL) forms of AD patients (P &lt; 0.01). AD patients with accompanied allergic diseases showed significantly higher tIgE levels than those without accompanied allergic symptoms (280 ± 286 IU/mL vs 194 ± 248 IU/mL). Conclusion: Neither sIgE nor tIgE levels can be used to evaluate the condition or severity of AD. AD patients with accompanied allergic diseases showed significantly higher tIgE levels than those without accompanied allergic symptoms. Infantile AD patients are more allergic to food, while adolescents and adults are more allergic to environmental antigens. IgE tests must be interpreted by combining with clinical history to avoid unnecessary food avoidance. Early food allergen introduction for infants may be promising for the prevention of food allergies.

Fluconazole worsened lung inflammation, partly through lung microbiome dysbiosis in mice with ovalbumin-induced asthma.

Innate immunity in asthma may be influenced by alterations in lung microbiota, potentially affecting disease severity. This study investigates the differences in lung inflammation and microbiome between asthma-ovalbumin (OVA) administered with and without fluconazole treatment in C57BL/6 mice. Additionally, the role of inflammation was examined in an in vitro study using a pulmonary cell line. At 30 days post-OVA administration, allergic asthma mice exhibited increased levels of IgE and IL-4 in serum and lung tissue, higher pathological scores, and elevated eosinophils in bronchoalveolar lavage fluid (BALF) compared to control mice. Asthma inflammation was characterized by elevated serum IL-6, increased lung cytokines (TNF-α, IL-6, IL-10), and higher fungal abundance confirmed by polymerase chain reaction (PCR). Fluconazole-treated asthma mice displayed higher levels of cytokines in serum and lung tissue (TNF-α and IL-6), increased pathological scores, and a higher number of mononuclear cells in BALF, with undetectable fungal levels compared to untreated mice. Lung microbiome analysis revealed similarities between control and asthma mice; however, fluconazole-treated asthma mice exhibited higher Bacteroidota levels, lower Firmicutes, and reduced bacterial abundance. Pro-inflammatory cytokine production was increased in supernatants of the pulmonary cell line (NCI-H292) after co-stimulation with LPS and beta-glucan (BG) compared to LPS alone. Fluconazole treatment in OVA-induced asthma mice exacerbated inflammation, partially due to fungi and Gram-negative bacteria, as demonstrated by LPS+BG-activated pulmonary cells. Therefore, fluconazole should be reserved for treating fungal asthma rather than asthma caused by other etiologies.

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.

IgE immunoadsorption: technical background, functionality, and first clinical experience

Summary Background The prevalence of allergic diseases has risen in the 21st century, drawing attention to specific therapeutic and preventive strategies. Due to the key role of immunoglobulin E (IgE) in the development of allergic reactions, IgE represents a key target treatment. In this scenario, IgE immunoadsorption (IgE-IA) has been investigated as a procedure that selectively removes circulating IgE antibodies from the bloodstream of patients with atopy. Methods This narrative review aims to critically summarize the current insights regarding IgE-IA in the context of the management of allergic diseases, ranging from the rationale to the technical aspects, as well as the benefits and unmet needs. Results IgE-IA might be a treatment strategy in well-selected patients with allergic diseases. IgE depletion through sessions of IgE-IA results in immediate clinical improvement and might be useful in acute situations when a rapid clinical response is required or when classic approaches are contraindicated or ineffective. Due to the reduced effectiveness over time, IgE-IA could be a valid first approach before starting another IgE depletion therapy, such as omalizumab, when its commencement would otherwise be contraindicated by too-high serum IgE levels. Conclusion Overall, IgE-IA is safe and well tolerated; however, this procedure is currently difficult to implement in routine clinical practice because of costs, time demands, need for hospitalization, and the invasiveness of the procedure, with the associated risks related to the necessity of venous catheterization.

Влияние избыточной массы тела и ожирения на спирометрические, гематологические показатели, уровень общего иммуноглобулина Е и интерлейкина-6 в сыворотке крови у детей и подростков с бронхиальной астмой

There is undoubtedly insufficient number of studies dedicated to the interleukin-6 (IL-6) in blood serum of children and adolescents with bronchial asthma (BA) and those are contradictory. Connection between the IL-6 serum level and systemic markers of type 2 inflammation in BA in children and adolescents depending on the nutritional status remains a subject to discussion as well. The purpose of this research was to study the effect of excess body weight (BW) and obesity on spirometric, hematological parameters, total immunoglobulin E (IgE), IL-6 levels in blood serum of children and adolescents with BA. Materials and methods used: a single-center observational cross-sectional pilot study of 76 adolescents aged 6 to 17 y/o (75% (57) boys) with BA was conducted. All were measured for anthropometric and spirometric parameters, body composition, hematological parameters, total IgE and IL-6 levels in blood serum. Dysanapsis was diagnosed when three conditions were simultaneously met: 1. high or high-to-normal zFVC (above 0.674), 2. normal zFEV1 (above -1.645), and 3. low FEV1/FVC index (below 80%). Results: the number of monocytes (109/l) in peripheral blood and the serum IL-6 level (pg/ml) were statistically significantly higher in the group of patients with overweight and obesity compared to patients with underweight/normal BW (0.55 [0.49; 0.77] v 0.51 [0.42; 0.58], p=0.043 and 1.99 [1.20; 5.78] v 1.28 [0.31; 2.43], p=0.002, respectively). In patients with excess BW and obesity, an inverse statistically significant relationship was found between the serum IL-6 level, zFEV1/FVC and the dysanapsis ratio (R=-0.53, p=0.009, R=-0.61, p=0.002, respectively). Conclusion: formation of an obstructive pattern in children and adolescents with BA with excess BW and obesity may be associated with non-T2-dependent inflammatory mechanisms.

Association of immunoglobulin E levels with glioma risk and survival.

Previous epidemiologic studies have reported an association of serum immunoglobulin E (IgE) levels with reduced glioma risk, but the association between IgE and glioma prognosis has not been characterized. This study aimed to examine how sex, tumor subtype, and IgE class modulate the association of serum IgE levels with glioma risk and survival. We conducted a case-control study using participants from the University of California, San Francisco Adult Glioma Study (1997-2010). Serum IgE levels for total, respiratory and food allergy were measured in adults diagnosed with glioma (n = 1319) and cancer-free controls (n = 1139) matched based on age, sex, and race and ethnicity. Logistic regression was adjusted for patient demographics to assess the association between IgE levels and glioma risk. Multivariable Cox regression adjusted for patient-specific and tumor-specific factors compared survival between the elevated and normal IgE groups. All statistical tests were 2-sided. Elevated total IgE was associated with reduced risk of IDH-wildtype (RR = 0.78, 95% CI: 0.71-0.86) and IDH-mutant glioma (RR = 0.73, 95% CI: 0.63-0.85). In multivariable Cox regression, positive respiratory IgE was associated with improved survival for IDH-wildtype glioma (RR = 0.79, 95% CI: 0.67-0.93). The reduction in mortality risk was significant in females only (RR = 0.75, 95% CI: 0.57-0.98) with an improvement in median survival of 6.9 months (P<.001). Elevated serum IgE was associated with improved prognosis for IDH-wildtype glioma, with a more pronounced protective effect in females than males, which has implications for the future study of IgE-based immunotherapies for glioma.

Treatment of refractory immune-mediated necrotizing myopathy with efgartigimod.

We aimed to explore the efficacy and safety of efgartigimod in patients with refractory immune-mediated necrotizing myopathy (IMNM). This open-label pilot observational study included seven patients with refractory IMNM, all of whom received intravenous efgartigimod treatment. The clinical response was assessed after 4 weeks of efgartigimod treatment according to the 2016 American College of Rheumatology-European League Against Rheumatism response criteria for adult idiopathic inflammatory myopathy. Serum levels of immunoglobulin as well as anti-signal recognition particle (SRP) and anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) antibodies were measured using enzyme-linked immunosorbent assays and commercial line immunoblot assays. Safety assessments included evaluations of adverse events and severe adverse events. The seven patients with refractory IMNM included five cases with anti-HMGCR antibodies and two cases within anti-SRP antibodies. Four of the seven patients achieved clinical responses. The total improvement score for the responders at 4 weeks were 32.5, 40.0, 47.5, and 70.0, and those at 8 weeks were 27.5, 47.5, 57.5, and 70.0. In comparison to the responsive patients, the non-responsive patients had longer durations [8 (-) versus 2 (1-5) years, P = 0.03], and more chronic myopathic features by muscle biopsy (67% versus 0%, P= 0.046). Serum immunoglobulin G levels (11.2 ± 2.5 versus 5.7 ± 2.5, P = 0.007) and anti-HMGCR/SRP antibody levels (97.2 ± 6.9 versus 41.8 ± 16.8, P = 0.002) were decreased after treatment compared with baseline levels. Adverse events were reported in one of the seven patients, who showed mild headache. Despite its small size, our study demonstrated that promoting the degradation of endogenous immunoglobulin G may be effective for patients with IMNM. Efgartigimod may be a promising option for cases of refractory IMNM to shorten duration and minimize chronic myopathic features.