International Archives of Allergy and Immunology最新文献

Introduction: Omalizumab is an effective add-on therapy for chronic spontaneous urticaria (CSU) refractory to antihistamines. However, biomarkers predicting treatment response remain unclear. This 10-year real-life, retrospective study aimed to assess the efficacy and safety of omalizumab in CSU and to identify predictors of treatment response, particularly focusing on total IgE levels.

Methods: We included 221 adult CSU patients treated with omalizumab between 2015 and 2024. Clinical response was evaluated using Urticaria Activity Score over 7 days (UAS7) and Urticaria Control Test (UCT). Treatment response was categorized as rapid, late, or non-response. Laboratory parameters, including total IgE, eosinophils, and thyroid autoantibodies, were analysed in relation to treatment outcomes.

Results: Omalizumab provided rapid or late responses in 98.2% of patients, with significant reductions in UAS7 and improvements in UCT scores over time. Only 1.8% were non-responders. A total IgE level ≤12.5 IU/mL was identified as a strong predictor of non-response (AUC: 0.903), with 75.0% sensitivity and 96.7% specificity. Multivariate logistic regression revealed that lower total IgE levels independently predicted non-response (OR: 0.032, p = 0.031).

Conclusion: Omalizumab is effective and safe in real-life CSU management, even among patients with comorbidities such as autoimmune diseases and malignancies. Low total IgE levels may serve as a reliable biomarker for predicting non-response and guiding individualized treatment strategies.

Introduction: Immunoglobulin E-mediated food allergies (FAs) is a growing concern in the Western world. Established risk factors include a personal or familial history of other atopic comorbidities, genetic predisposition, male sex, and hygienic environment. However, these factors fail to explain most FA cases. The study aimed to discover additional risk factors for FA by analyzing a large database.

Methods: This retrospective study utilized data from Clalit Health Services, Israel's largest healthcare provider. Employing explainable artificial intelligence methods, the investigation sought to identify variables in the first 6 months of life and parental factors correlated with FA diagnosis, among children born from January 1, 2006, to August 31, 2021.

Results: The analysis encompassed 370,298 children, with FA diagnosed in 6,911 infants (1.87%). Key findings revealed that high socioeconomic score (SES) (relative risk [RR] = 9.92), Jewish origin (RR = 3.83), and personal history of atopic dermatitis (RR = 5.3) were the most significant variables associated with FA development. Other variables with lesser correlation strength included parental atopic comorbidities, blood type, and antibiotics and anti-acid drugs use. Surprisingly, prematurity and birthweight <2,500 g were correlated with a lower risk of FA development.

Conclusions: The correlations found between those variables and FA do not explain most FA cases. Moreover, the impact of SESs and ethnicity might be explained by differences in cultural behaviors that influence the development of FA. This could not be determined as data such as the age of allergenic foods introduction were unavailable in the database. Further investigation is warranted to establish causal links and the clinical significance of these suggested risk factors.

Background: Asthma is a chronic disease characterized by airway inflammation, oxidative stress, and bronchial hyperresponsiveness. Quercetin, a safe and well-tolerated flavonoid, reduces airway inflammation and has antioxidant effects, which are partly modulated by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. This dual anti-inflammatory and antioxidant pharmacological effect makes this compound a potentially effective therapeutic agent. We used primary human bronchial epithelial cells (HBECs) from asthmatic and healthy controls to evaluate whether quercetin modulates Nrf2 expression and reduces inflammatory cytokines.

Methods: Differentiated ciliated and mucus-producing HBECs were maintained for 21 days at the air-liquid interface (ALI), then were pretreated for 18 hours with 25 µM quercetin. Following a washout with phosphate-buffered saline, cells were exposed to IL-13 (10 ng/mL) for 3 hours. Cell culture supernatants were collected, and a cytokine panel was measured. Additionally, bulk RNA-seq differential expression testing was performed, where a significant between-group difference was defined by a false discovery rate (FDR) < 0.05 and an absolute value of the log2 fold change > 0.5 Results: Human airway epithelial cells treated with quercetin showed a significant increase in Nrf2 protein levels compared to untreated cells (p=0.008). In addition, quercetin treatment was associated with a reduction in TNF-α expression in asthmatic cells. Although this decrease did not reach statistical significance, the observed trend may suggest a potential anti-inflammatory effect worth further investigation. Moreover, compared to control, quercetin significantly upregulated the gene expression of the γ-glutamate-cysteine ligase catalytic subunit (GCLC) subunit and NAD(P)H quinone oxidoreductase-1 (NQO1) (p=0.009 and p=0.04 respectively) in cultured HBECs.

Conclusion: This study suggests that quercetin may be a promising therapeutic agent to improve health outcomes in asthma by activating the Nrf2 pathway to reduce oxidative stress and pro-inflammatory cytokines in airway epithelium, which warrants further mechanistic and clinical investigation.

Introduction: Eosinophilic esophagitis (EoE) is a chronic esophageal disorder associated with atopy. However, there are few data on prevalence of EoE in atopic patients. We aimed to determine the prevalence of EoE in atopy and associated demographics, risk factors, and symptoms.

Methods: A cross-sectional study was conducted with data from the VA population, 2009-2021, using a 9.7% random sample from a nationwide database. Demographics, symptoms, and risk factors were collected on patients at least one atopic condition. Logistic regression models for EoE, allergy, and symptoms were developed.

Results: Of 1,110,189 VA patients, 26% (288,193) had at least one atopic condition and 0.092% (1,022) had an EoE diagnosis. In atopic patients, EoE was most common in patients with milk (4.10%), egg (1.06%), and wheat (0.81%) allergy. Frequency of EoE was lower in patients with asthma (0.26%) and rhinitis (0.22%). Compared to male VA patients without allergy, odds ratio (OR) for EoE was 2.87 for an atopic male, and 3.29 for an atopic female. ORs were increased for EoE in those with milk allergy (OR = 19.9), wheat allergy (OR = 5.94), and egg allergy (OR = 4.10). Of patients with more than one allergic condition, rhinitis and asthma were most likely to increase odds of EoE.

Conclusion: The prevalence of EoE is substantially increased in atopic patients, and in particular in patients with food allergy. There should be high clinical suspicion for EoE in a patient with atopic disease and especially milk, wheat, or egg allergy.

Background: Chronic urticaria (CU) is an inflammatory skin disease characterized by aberrant mast cell (MC) activation. Notably, 30% of patients show poor response to existing therapies. The competitive endogenous RNA (ceRNA) network has emerged as a key regulator of MC signaling, but the hierarchical regulatory mechanisms underlying this process remain incompletely understood.

Summary: This review systematically analyzed PubMed and Web of Science literature (2000-2024) using keywords linking CU, ceRNA/long-stranded non-coding RNA/circular RNA, and MCs. It proposes a three-tiered regulatory model of the ceRNA network in maintaining sustained MC activation: (1) core RNAs (e.g., NEAT1) adsorb microRNAs (miRNAs) to deregulate key signaling pathways; (2) shared miRNAs (e.g., miR-155) act as bridges between upstream and downstream targets; and (3) effector molecules (e.g., STAT3) drive MC activation. RNA-based therapeutics and exosome delivery technologies targeting these regulatory axes may offer new strategies for refractory CU.

Key messages: (1) The ceRNA network orchestrates MC activation through hierarchical regulation of core RNAs, shared miRNAs, and effector molecules. (2) Targeting ceRNA-mediated pathways holds promise for developing precision therapies for CU, particularly in patients unresponsive to conventional treatments. (3) Translational approaches using RNA therapeutics or exosome systems may address therapeutic gaps in refractory cases.

Introduction: Chronic spontaneous urticaria (CSU) presents as repetitive spontaneous hives and/or angioedema lasting for at least 6 weeks. In contrast, chronic inducible urticaria (CIndU) is triggered by specific stimuli. This study aimed to characterize children who have concurrent CSU and CIndU excluding children with symptomatic dermographism and to identify factors that distinguish them from children with CSU alone or CIndU alone.

Methods: This prospective cohort study was conducted over an 11-year period, from 2013 to 2024, at Montreal Children's Hospital in Canada. It included pediatric patients aged 0-18 years with chronic urticaria.

Results: During the study period, 202 pediatric patients with chronic urticaria were included. Of these, 20 patients (9.9%) had both CSU and CIndU concomitantly. Cold urticaria was the most common CIndU associated with concomitant urticaria group, affecting 9 patients (45%). The mean age of patients with concomitant urticaria was 6.2 years (IQR: 5.0-11.8), and the majority were females (60%). Eight patients (42%) initially presented with CSU alone. Uncontrolled CSU (baseline UAS7 scores ≥16) was more common in patients with concomitant urticaria (60%) versus those with isolated CSU (27.5%) or CIndU (17.2%) (p < 0.01). Omalizumab usage was significantly higher in children with concurrent CSU and CIndU (20%) compared to those with CSU alone (5.9%) or CINDU alone (0%) (p = 0.04 and 0.01, respectively).

Conclusion: Pediatric patients who have concomitant CSU and CIndU represent a more severe CU phenotype that requires the use of biologics like omalizumab as compared to children with CSU/CIndU alone.

Introduction: Allergic diseases represent a growing global health challenge, necessitating region-specific allergen characterization for targeted prevention and treatment. This study aimed to analyze the characteristics of allergens in patients with allergic diseases in Sanmen, Zhejiang Province.

Methods: A retrospective analysis was performed on allergen test results obtained from patients with allergic diseases who attended the People's Hospital of Sanmen County, Zhejiang Province, from July 2019 to June 2023. The serum total IgE levels and allergen-specific IgE (sIgE) positivity rates were assessed, and intergroup differences were statistically analyzed using hypothesis testing methodologies.

Results: A comprehensive analysis of 19,598 patients with allergic diseases was conducted, evaluating serum total IgE levels and sIgE positivity rates. The positivity rate for serum total IgE was 25.67%, significantly higher than the IgE prevalence of inhalant allergens (24.84%) and food allergens (12.48%), significantly higher than the positivity rate for food allergen sIgE at 12.48% (p < 0.001). Dermatophagoides spp. allergens were identified as the primary source of inhalant allergens with a positivity rate of 16.31%, whereas crustacean allergens (tropomyosin) were the most prevalent food allergen with a positivity rate of 5.17%. The positivity rates for serum total IgE and sIgE were significantly higher in males compared to females (p < 0.001). Although females exhibited a higher positivity rate for dog hair allergy, the difference was insignificant (p = 0.306). The serum total IgE positivity rate was highest in the ≤12 age group and declined with age, with a resurgence observed in individuals over 60. Similarly, the positivity rates for Dermatophagoides spp. allergens and cow's milk also decreased with age. The highest incidence of allergic diseases occurred between August and November, peaking in November at 30.63%. Among patients with allergic diseases, 23.20% tested positive for at least one sIgE, while 3.17% demonstrated positivity for three or more allergens.

Conclusion: In Sanmen, Zhejiang, Dermatophagoides spp. allergens were identified as the principal inhalant allergen among patients with allergic diseases, whereas crustacean allergens (tropomyosin) were the predominant food allergen. Male patients demonstrated a higher allergen positivity rate compared to females. These findings, derived from allergen screening, establish a solid foundation for laboratory diagnostics, thereby aiding in the prevention, diagnosis, and treatment of allergic diseases.

Background: Chronic spontaneous urticaria (CSU) pathogenesis is unclear, with autoimmune and autoallergic mechanisms implicated. Many CSU patients have an atopic background, and group 2 innate lymphoid cells (ILC2s) are involved in atopic and autoimmune diseases, but their role in CSU is unknown.

Objectives: This study investigated ILC2s levels in CSU patients, analyzed their correlation with clinical features, and explored ILC2s' potential role in CSU pathogenesis.

Methods: Peripheral blood samples from 68 CSU patients and 53 healthy controls were collected. ILC2s levels in peripheral blood mononuclear cells (PBMCs) were measured using flow cytometry, and correlations with clinical features were analyzed.

Results: CSU patients had significantly lower peripheral blood ILC2s levels than healthy controls (p<0.0001). In the CSU group, autologous serum skin test (ASST)-negative patients had higher ILC2s levels than ASST-positive patients (p=0.0053), and atopic CSU patients had higher ILC2s levels than non-atopic CSU patients (p=0.024). However, no significant associations were found between ILC2s levels and disease activity, duration, response to H1-antihistamine therapy, or clinical manifestations like dermographism or angioedema.

Conclusion: Reduced peripheral ILC2s levels in CSU may indicate autoimmune dysregulation. While comparaed with non-atopic CSU, the elevated ILC2s in atopic CSU suggest distinct type 2 inflammatory pathways. Yet, ILC2s don't correlate with clinical severity or treatment response, implying their likely immunomodulatory role in CSU pathogenesis related to autoimmune and atopic mechanisms, not as disease biomarkers. Further research is needed to clarify their exact function and therapeutic potential.

Introduction: Henoch-Schönlein purpura (HSP) is a systemic vessel vasculitis characterized by IgA- and complement-mediated vascular injuries. However, the precise mechanisms underlying disease progression and severity remain unclear. This study aimed to identify inflammation-related proteins and pathways associated with HSP and disease severity.

Methods: Plasma samples from 10 patients with HSP and 10 healthy controls (HC) were analyzed using the Olink inflammation panel. Patients were categorized into simple purpura (HSP_S) and complex purpura (HSP_C) groups based on clinical manifestations. Clinical and laboratory characteristics were also collected for analysis.

Results: Patients in HSP_C group showed significant higher level of 24-h urine protein quantification (p = 0.038). Among the 92 inflammation-related proteins analyzed, 13 were differentially expressed between patients with HSP and HC. Notably, Oncostatin M (OSM), interleukin-6 (IL-6), and transforming growth factor-α (TGF-α) were significantly elevated in HSP patients. Compared with the HSP_S group, HSP_C group exhibited increased levels of fibroblast growth factors (FGF19), glial cell line-derived neurotrophic factor, HGF, and OSM. Pathway enrichment revealed upregulation of the JAK-STAT and PI3K-Akt signaling pathways in HSP_C group, suggesting their involvement in disease severity. Protein-protein interaction analysis identified OSM, IL-6, TGF-α, and IL-18 as key inflammatory hubs, with OSM showing the strongest correlation with systemic injury.

Conclusions: This study provides novel insights into the inflammatory proteomic landscape of HSP patients, highlighting OSM as a potential biomarker of disease severity and systemic injury. The JAK-STAT and PI3K-Akt pathways may play central roles in HSP pathogenesis and represent potential therapeutic targets.

Background: Microplastics (MPs) constitute an emerging category of environmental pollutants that have attracted considerable scientific scrutiny due to their widespread global distribution and documented health hazards. Importantly, these particles pose a threat to human health by disrupting epithelial barriers, which in turn heightens susceptibility to allergic sensitization and exacerbates pre-existing allergic conditions.

Summary: This review consolidates contemporary evidence regarding the involvement of MPs in allergic diseases, focusing on their principal sources, such as environmental degradation and consumer products, as well as their exposure pathways, including inhalation, ingestion, and dermal contact. It elucidates the mechanisms by which MPs provoke immune disturbances - specifically Th2 polarization, alarmin release, and oxidative stress - that collectively contribute to allergic inflammation. Furthermore, the analysis underscores the epidemiological correlation between MPs and the increased incidence and severity of asthma, allergic rhinitis, and atopic dermatitis, in alignment with the epithelial barrier hypothesis.

Key messages: MPs compromise epithelial barriers and promote type 2 inflammation. There is an urgent need to elucidate dose-dependent immunotoxicological mechanisms. Evidence-based policies are required to mitigate exposure and allergy burden.