International Archives of Allergy and Immunology最新文献

Introduction: Nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity is a heterogeneous condition with diverse clinical phenotypes. Although age-related changes in immune and inflammatory pathways have been proposed, systematic evaluations of age-associated phenotypic differences remain limited.

Methods: Between 2019 and 2025, 1,363 patients evaluated for suspected drug hypersensitivity were screened, and 484 adults with clinically defined NSAID hypersensitivity were retrospectively analyzed. Patients were categorized as early-onset (<40 years) or late-onset (≥40 years). Reaction phenotypes were classified retrospectively according to EAACI/ENDA criteria. Demographic characteristics, comorbidities, reaction phenotypes, and laboratory parameters, including total IgE levels and eosinophil counts, were compared. Subgroup analyses assessed the association between chronic low-dose aspirin use and clinical features. Multivariate logistic regression was performed to identify independent predictors of late-onset hypersensitivity.

Results: The median age of the cohort was 41 years, and 65.7% were female. Cutaneous reactions were most common (66.5%), followed by cutaneous-respiratory (19.0%) and systemic reactions (8.7%). Late-onset patients (n = 258) exhibited significantly higher prevalences of asthma (19.8% vs. 8.0%; p < 0.01) and cardiovascular disease (10.5% vs. 1.3%; p < 0.001). Chronic low-dose aspirin use was more frequent in late-onset cases (14.3% vs. 1.3%; p < 0.001) and was associated with increased respiratory involvement. In multivariate analysis, asthma (OR 2.48, 95% CI 1.30-4.73; p = 0.006) and low-dose aspirin use (OR 7.52, 95% CI 1.71-32.50; p = 0.008) independently predicted late-onset NSAID hypersensitivity.

Conclusion: NSAID hypersensitivity exhibits distinct age-related clinical phenotypes, with a higher burden of respiratory involvement and comorbid disease in late-onset cases. Chronic low-dose aspirin use is strongly associated with this phenotype. Recognition of age-associated patterns may support improved clinical risk stratification and individualized management strategies.

Background: Atopic dermatitis (AD) is a common inflammatory skin condition characterized by epidermal barrier dysfunction and immune dysregulation, affecting both children and adults.

Objectives: This study aimed to determine the prevalence of common allergen sensitizations in patients with AD, compared with controls without allergic diseases, and to identify those associated with an increased risk of asthma or allergic rhinitis.

Methods: We conducted a cross-sectional study including patients with atopic dermatitis and age- and sex-matched controls selected by propensity score matching from the Center of Allergy and Clinical Immunology, Vinmec Times City Hospital. Total IgE levels and specific IgE sensitization to common allergens were documented using an extract-based multiplex assay.

Results: Both the AD and control groups each comprised 452 patients and were comparable in age, median (IQR, range): 7 (1-29, 0-84) and sex distribution (51.11% female). Sensitization to at least one allergen was observed in 59.51% of patients, with a mono-sensitization rate of 11.73% and a poly-sensitization rate of 47.79%. House dust mites had the highest sensitization rates among AD patients in our study, with sensitization rates for Dermatophagoides pteronyssinus, Dermatophagoides farinae, and Blomia tropicalis at 29.65%, 26.99%, and 11.5%, respectively. Eggs and milk were the most common food allergens, with sensitizations rates of 20.58% and 12.61%, respectively. Although sensitization rates were high, the prevalence of true clinical allergy was much lower, underscoring the need for cautious interpretation of test results in conjunction with clinical symptoms. Age-related differences were evident: younger children were more often sensitized to food allergens, older children and adolescents to respiratory allergens, and elderly patients to cockroach, and Candida albicans. Additionally, sensitization to C. albicans, D. pteronyssinus, D. farinae, cat dander, dog dander, rice grain, barley flour, and rye flour was significantly more frequent in patients with AD compared to individuals with no allergic diseases. Such sensitization was also associated with a higher risk of respiratory allergic comorbidities, suggesting the potential role of these allergens as distinctive markers of atopy.

Conclusion: This study highlights the importance of understanding allergen sensitization in patients with AD to optimize management strategies, particularly in Vietnam, where house dust mite sensitization is highly prevalent. Allergen avoidance and allergen-specific immunotherapy could be beneficial as add-on therapies for AD.

Introduction: Understanding the effects of age and sex on circulating cytokine and chemokine levels in healthy individuals is essential for establishing reliable reference ranges and tailoring assessments. Although previous studies have compared younger and older populations, few have systematically examined sequential age decades. This study aimed to characterize continuous age-related changes in serum cytokine and chemokine profiles across adulthood in 157 healthy individuals.

Methods: Serum samples from 100 individuals aged 20s-60s (10 males and 10 females per decade) were obtained from the Japanese Red Cross Society. Additional samples from 57 individuals aged 60s-80s (17-20 per decade) were included. Concentrations of 26 cytokines and chemokines were measured using a multiplex bead-based immunoassay. Associations between analyte levels and age were assessed using the Jonckheere test and Spearman's rank correlation. Sex differences were evaluated using Student's t-test. A two-sided p value < 0.05 was considered statistically significant.

Results: Three distinct age-related patterns were identified. Type 1 demonstrated continuous trends from the 20s to the 80s: IL-2, IP-10, TARC, and granulysin increased significantly with age, whereas TGF-β, FGF-2, and fractalkine decreased significantly. Type 2a (IFN-γ, IL-17, and IL-15) showed significant declines from the 20s to the 60s but an overall increase from the 20s to the 80s. Type 2b included IL-12p70, TNF-α, IL-10, IL-5, and IL-7, which increased significantly from the 20s to the 80s, and IL-8, which decreased; however, no significant trends were observed between the 20s and 60s. Type 2c (IL-6 and IL-1Ra) increased significantly from the 20s to the 60s but showed no significant trend across the 20s-80s. Between the 20s and 60s, IL-15, IL-1Ra, TGF-β, and IP-10 were significantly higher in females, whereas IL-8 and granulysin were higher in males. Across the 20s-80s, only IL-1Ra and TGF-β remained higher in females, and IL-8 remained higher in males.

Conclusions: Certain cytokines exhibited consistent age- and gender-related trends, whereas others varied between the 20s-60s and the 20s-80s.

Introduction: Japanese cedar pollinosis (JCP) is highly prevalent in Japan, and sublingual immunotherapy (SLIT) remains one of the few effective disease-modifying treatments. While many patients have significant benefits, biomarkers predicting SLIT responsiveness are lacking. Single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) identified the ribosomal protein gene RPS26 as a candidate associated with treatment response. This study aimed to determine whether RPS26 expression contributes to SLIT efficacy and to define its involvement in T-cell dynamics, cytokine production, and epigenetic regulatory pathways.

Methods: PBMCs from 35 patients with JCP were analysed before SLIT, and paired samples from seven patients were evaluated after 1 year of SLIT. scRNA-seq was performed in four responders and three non-responders. Changes in T-cell subsets and interleukin (IL)-5 and IL-10 secretion were evaluated during SLIT. Functional relevance was examined through small interfering RNA-mediated RPS26 knockdown followed by allergen stimulation. The relationship between RPS26 and the ten-eleven translocation family (TET2 and TET3) expression was assessed by quantitative PCR.

Results: scRNA-seq revealed significant RPS26 upregulation in responders. Although bulk RPS26 expression did not differ between responders and non-responders, all subjects with high RPS26 expression (≥100 relative units) were responders. SLIT increased follicular regulatory and type 1 regulatory T-cells in responders, whereas IL-10 elevation occurred exclusively in high-RPS26 responders. RPS26 knockdown enhanced early apoptosis and cell death, and reduced IL-10 expression following allergen challenge. RPS26 expression was strongly correlated with the epigenetic regulators TET2 and TET3, both essential for regulatory T-cell stability.

Conclusion: RPS26 appears to function as both a biomarker and a contributor to immune tolerance during SLIT. Its association with IL-10 induction, regulatory T-cell expansion, apoptosis resistance, and TET2/TET3 expression suggests a translational-epigenetic axis supporting allergen desensitization. These findings highlight ribosomal specialization as a determinant of immunotherapy responsiveness. Larger studies are needed to validate RPS26 and further define its mechanistic role in allergen-specific immunotherapy.

In the article "Adipose Tissue-Derived Mesenchymal Stem Cells Regulate Th17/Treg Cells in a Rat Model of Allergic Rhinitis by Activating IL-2/JAK-3/STAT-5 Signaling Pathway" [Int Arch Allergy Immunol. 2025;186:811-823; https://doi.org/10.1159/000543758] by Hou et al., the funding information was incorrectly given. The correct funding information should read as follows:Funding SourcesThis research was supported by the Scientific Research and Innovation Fund Project of Gansu University of Chinese Medicine (2020KCZD-7), Lanzhou Talent Innovation and Entrepreneurship Project (2021-RC-129), Gansu Province Health Industry Outstanding Young Talent Project (GSWSQN2021-002), National Natural Science Foundation of China (82260475), and Key Project of the National Research Project Cultivation Plan of Gansu Provincial People's Hospital (19SYPYA-13). This work was supported by the Hospital Fund of The First Hospital of Lanzhou University (ldyyyn2021-70), Natural Science Foundation of Gansu Province (24JRRA1081), Natural Science Foundation of Gansu Province (21JR1RA153), Natural Science Foundation of Gansu Province (21JR7RA363), Natural Science Foundation of Gansu Province (23JRRA1634), and Cuiying Scientific Training Program for Undergraduates of The Second Hospital Clinical Medical School, Lanzhou University (20210050006).

Influenza, commonly known as the flu, is a contagious respiratory illness caused by influenza viruses, primarily affecting the epithelial cells of the respiratory tract. There are several strains of the virus, with influenza A and B being the most significant in terms of public health impact. The immune system's response to influenza infection plays a crucial role in determining the severity of the illness and the effectiveness of vaccination strategies. The immune system's response to the influenza virus is both complex and vital for recovery and immunity. Vaccination plays a key role in mitigating the impact of influenza, although its effectiveness can vary based on multiple factors. Continuous monitoring of circulating strains and advancements in vaccine technology are essential in improving prevention strategies and protecting public health. Ongoing research into novel vaccine strategies is crucial for achieving better efficacy and addressing vaccine hesitancy, ultimately leading to reduced morbidity and mortality associated with influenza. Key words: Influenza, TLRs, CTL, PRR, NK.

Background: Haemophagocytic lymphohistiocytosis (HLH) is a potentially life-threatening, multisystemic, hyperinflammatory disease. There is a trend towards increased reports of drug-induced HLH (diHLH), an entity that has some features akin to severe cutaneous adverse reactions (SCAR).

Objective: To provide a summary of the literature on reported cases of diHLH.

Methods: A narrative review of diHLH cases published between January 1993 and August 2023 was undertaken. All potential confounding secondary causes of HLH, as well as cases attributed to immune checkpoint inhibitors, chimeric antigen receptor T-cell immunotherapy, and vaccines, were excluded from the analysis.

Results: There were thirty-nine cases identified, with a median age of 28.0 years (IQR 7-46), and a predominance of males (57.9%). Anticonvulsants (n=15, 38.4%), particularly lamotrigine (n=10, 66.7%), and antimicrobials (n=15, 38.4%) were most frequently implicated. Among the antimicrobials, beta-lactam antibiotics were the most common (n=12, 80%). Time to latency for presentation of diHLH was 14 days (IQR 8-21); anticonvulsants had a significantly longer latency (17 days) than antimicrobials (12.5 days; p=0.0180). The median HLH-1994/2004 diagnostic criteria and H-score were 5 and 227, respectively. Ten patients (25.6%) also had SCAR features at initial presentation (DRESS syndrome: n=7 and Stevens-Johnson Syndrome and/or Toxic epidermal necrolysis: n=3). Nine patients (23.1%) succumbed to the disease, who were significantly older (median age of 56 years) compared to those achieving remission (median age of 27.5 years, p=0.0092).

Conclusion: Drug-induced HLH is a rare but important diagnosis sharing some similarities in its initial presentation with SCAR, including anticonvulsants and antimicrobials as culprit drugs. As diHLH mortality parallels that in other forms of secondary HLH, prompt recognition is required for culprit drug cessation and initiation of immunosuppressive treatment.

Background: Eosinophilic esophagitis (EoE) is a chronic, immune-mediated esophageal disease increasingly recognized in children. Despite growing awareness, diagnostic delays, heterogeneous presentations, and variable treatment responses continue to complicate management.

Objective: This study aimed to describe the real-world clinical characteristics, atopic features, treatment patterns, and long-term outcomes of children with EoE, and to identify practical challenges that may inform more effective management strategies.

Methods: This retrospective study included 50 children diagnosed with EoE between October 2020 and October 2025 at a tertiary pediatric center. Demographic, clinical, endoscopic, histopathological, and allergic data were reviewed. Symptom burden and adaptive behaviors were evaluated using the Gazi Eosinophilic Esophagitis Symptom and Adaptation Scale (GaziESAS).

Results: Of the 50 patients, 33 (66%) were male. The median diagnosis age of 10.5 years with an estimated diagnostic delay of 1.6 years. At least one concomitant atopic disease was present in 36 patients (72%), most commonly allergic rhinitis in 24 (48%) and asthma in 16 (32%). Food sensitization was detected in 15 of 47 evaluated patients (31.9%), and patch test positivity in 15 of 49 patients (30.6%). All patients initially received proton pump inhibitors; topical corticosteroids and/or elimination diets were added as needed. Older age at diagnosis correlated with higher total GaziESAS scores (r = 0.524, p < 0.001), mainly due to adaptive behaviors (ρ = 0.457, p = 0.001). Females showed higher peak eosinophil counts than males (82.3 ± 37.3 vs. 49.6 ± 25 eos/HPF, p = 0.001). Complete histologic remission-defined as <15 eosinophils per high-power field in all follow-up endoscopies after the diagnostic procedure-was achieved in 25 patients (50%).

Introduction: O. fragrans flower is a highly popular edible flower due to its long-lasting aroma. Although it has been reported to possess multiple activities, no study focused on its effects on Mrgpr-mediated mast cell activation.

Methods: The ethanol extract of O. fragrans flower (OFE) was prepared and the analyzed by the NaNO2-Al(NO3)3-NaOH colorimetric method and HPLC. Compound 48/80 (C48/80) was used for activating Mrgpr signaling. Supernatant β-hexosaminidase level was assayed by using the fluorescence probe 4-Methylumbelliferyl N-acetyl-β-D-glucosaminide. The levels of cytoplasmic Ca2+ (Ca2+[c]) and intracellular mitochondrial Ca2+ (Ca2+[m]) were determined by fluorescence probes Fluo-3 AM and rhod-2/AM, respectively. The Ca2+ level outside the mitochondria was indicated by the fluorescence probe Calcium Green-5N. C48/80-induced vascular leakage, scratching behavior, and hypothermia models were used for evaluating the in vivo effects of OFE.

Results: The highly water-soluble flavonoid-rich OFE significantly inhibited C48/80-induced degranulation in LAD2 cells and primary rat peritoneal mast cells (RPMCs). It could rapidly and reversibly decrease Ca2+[c] level independent of the activation of Mrgpr signaling. Among four classical pathways responsible for Ca2+[c] removal, OFE failed to affect PMCA, SERCA, and NCX, but promoted the uptake of mitochondrial Ca2+. In vivo, OFE alleviated C48/80-induced vascular leakage, scratching, as well as hypothermia.

Conclusion: This study indicates, for the first time, that OFE is a mast cell stabilizer. It decreases Ca2+[c] to suppress mast cell degranulation by directly enhancing mitochondrial Ca2+ uptake. These findings may unveil a potential medicinal value of O. fragrans flower as a promising candidate for relieving mast cell activation-related diseases.

Background: Mucopolysaccharidosis type IVA (MPS IVA) is an ultra-rare lysosomal storage disease treated with enzyme replacement therapy (ERT) using Elosulfase alfa (ELA). However, ELA may induce immediate hypersensitivity reactions (I-HSRs), including anaphylaxis, and data on ELA-induced I-HSRs and rapid drug desensitization (RDD) are limited.

Objective: This study aimed to evaluate the frequency, phenotypes, risk factors, and desensitization outcomes of ELA-induced I-HSRs in children with MPS IVA.

Methods: Medical records of patients with MPS IVA between April 2004 and July 2023 were analyzed. I-HSRs were classified as Type I, cytokine-release syndrome (CRS), or mixed-type. Diagnostic testing and RDD protocols were evaluated. Logistic regression and receiver operating characteristic (ROC) analyses identified predictors of I-HSR occurrence.

Results: Thirty-one patients were included (48% male); the median age at diagnosis was 45 months (6-203) and follow-up 109 months (1-234). ERT was given to 25 patients (81%) for a median of 66 months (1-98). I-HSRs occurred in 28%: 71% Type I (all anaphylaxis), 14% mixed, and 14% CRS; all were moderate to severe. Patients with I-HSRs had a significantly lower age at diagnosis (p = 0.021); diagnosis ≤30 months predicted I-HSR (AUC = 0.80; sensitivity 71.4%, specificity 83.3%, OR 12.5; p = 0.016). Four patients underwent 490 RDDs with only one mild breakthrough reaction (0.2%).

Conclusion: ELA-induced I-HSRs are relatively frequent in MPS IVA, occur predominantly as Type I phenotypes, and are clinically significant. Younger age at diagnosis (≤30 months) markedly increases the risk of I-HSRs, and RDD is safe and effective long-term.