International Archives of Allergy and Immunology最新文献

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.

Introduction: Patients with infectious mononucleosis are often treated with penicillins, frequently resulting in maculopapular rashes resembling delayed drug hypersensitivity reactions (DHR). While traditionally considered self-limiting with no long-term consequences, some individuals develop persistent drug allergy. This study assessed the rate of persistent penicillin allergy in patients with a prior Epstein-Barr virus (EBV)-related penicillin-induced rash.

Methods: We retrospectively reviewed adolescent and adult patients, who developed an EBV-related rash after penicillin treatment and later underwent drug allergy testing between 2012 and 2023. Among 3,067 screened patients with suspected delayed DHR after penicillin, 15 fulfilled inclusion criteria (informed consent, confirmed EBV, and complete allergy workup). Clinical data, test results, and re-exposure history were extracted from a hospital record database.

Results: Fifteen patients were included (median age 18.5 years, 87% female). Skin tests were positive in 7 out of 15 subjects (47%). Four patients were re-exposed to penicillins before testing; 3 developed recurrent DHR, including 1 case with an acute generalized exanthematous pustulosis. Median time to allergy workup was 16 months. Positive skin tests were more common in those with prolonged DHR.

Conclusion: Nearly half of patients with EBV-related rashes after penicillin exposure showed evidence of persistent drug allergy, even years after the initial reaction. These findings emphasize the importance of allergy testing in patients with EBV-related DHR to prevent unnecessary antibiotic restrictions and avoid unintended re-exposures.

Introduction: Helminths' products modulate the allergic response. We aimed to analyze the inhibitory effect of Ascaris lumbricoides, Anisakis simplex, and A. simplex excretion/secretion (E/S) antigens in a peanut-induced anaphylaxis mouse model.

Methods: Four groups of nine C3H/HeOuJ mice were weekly sensitized with intraperitoneal (i.p.) peanut extract (P) for 3 weeks. Concomitantly, first group was daily treated with i.p. A. simplex somatic extract, second group with A. lumbricoides somatic extract, third group with A. simplex E/S extract (P/AK-ES), and a fourth group with saline (P/saline). Nine more mice were non-sensitized (i.p. saline) and used as control group (N/saline). After 5 weeks, anaphylaxis was induced with i.p. peanut extract and evaluated by the recognition of clinical symptoms and body temperature measurements. Specific IgG1, IgG2a, and IgE and cytokines were measured.

Results: Non-treated peanut-sensitized mice developed anaphylactic reactions following antigen challenge. Helminth crude extract-treated groups presented moderate symptoms. Nevertheless, P/AK-ES mice almost abolished the anaphylactic symptoms and impeded temperature drop after the challenge. All peanut-sensitized mice developed peanut-specific immunoglobulins. Helminth-treated groups showed an increase of specific IgG1 and IgG2a that peaked on weeks 3 and 4. By contrast, A. simplex E/S extract that hampered the production of specific IgE was observed in mice. Cytokines revealed a significant decrease in IL-5 and a significant increase in IL-10 and IFN-γ in the P/AK-ES group.

Conclusions: A. simplex E/S antigens have a potent and effective restraining effect on modulating peanut-induced anaphylaxis in mice.

Introduction: Interleukin 18 receptor 1 (IL18R1) is involved in the pathogenesis of asthma and atopic phenotypes. However, IL18R1 expression level in induced sputum supernatant of asthma remains unclear.

Methods: IL18R1, IL-4, IL-5, IL-13, IFN-r, and MUC5AC level in induced sputum supernatant was detected by ELISA in patients with asthma, and the correlation of IL18R1 expression with clinical parameters (FeNO, peripheral blood eosinophil count, serum IgE, and lung function), Th1 cytokine (IFN-r), T helper cell 2 (Th2) cytokine (IL-4, IL-5, and IL-13), and mucus (MUC5AC) were analyzed. Asthma subjects were categorized as IL18R1low and IL18R1high (below or above the upper quartile of the control group, respectively). Clinical features were compared between the IL18R1low and IL18R1high asthma subgroups. Subjects with asthma underwent a 4-week treatment with inhaled budesonide.

Results: We found that IL18R1 level in induced sputum increased and was correlated with FeNO, peripheral blood eosinophil count, serum IgE, FEV1 (%predicted), FEV1/FVC%, and Th2 cytokine (IL-4, IL-5, and IL-13) in patients with asthma. IL18R1 expression was not correlated with Th1 cytokine IFN-r and MUC5AC in induced sputum. IL18R1high asthma had higher FeNO levels, higher peripheral blood eosinophil counts, lower FEV1/FVC%, and higher Th2 cytokine (IL-4, IL-5, and IL-13) expression than IL18R1low subgroup or controls. IL18R1high asthma had a significant decrease in FeNO and more improvement in FEV1 during inhaled corticosteroid (ICS) treatment compared with patients having the IL18R1low subgroup.

Conclusions: IL18R1 level in induced sputum was increased. IL18R1low and IL18R1high asthma subgroups had different clinical features and responses to ICS treatment. IL18R1 level in induced sputum may be a novel marker of Th2-high asthma and has potential application in predicting treatment response.