International Archives of Allergy and Immunology最新文献

Introduction: The proportion of patients with pollinosis is relatively high within the allergic disease population. Climate change and air pollution negatively affect allergic respiratory diseases. Therefore, further studies are necessary to clarify the effects of pollen grains and air pollution on allergic diseases.

Methods: Building on our previous research, we established an Artemisia pollen-sensitized mouse model and evaluated the impact of nano-SiO₂ particle exposure on pollen allergy in this study. Serum samples were collected to detect specific IgE levels and cytokines and conduct metabolomic analysis. Single-cell suspensions were prepared from mouse spleens, and the Th1/Th2 cell ratio was analyzed by flow cytometry. We utilized RBL-2H3 cells, mouse bone marrow-derived mast cells (BMMCs), and the passive cutaneous anaphylaxis (PCA) model to investigate the effects of the most significant metabolites on allergic reactions.

Results: Exposure to nano-SiO₂ particles can exacerbate the damage to the nasal mucosal epithelial cells of pollen-sensitized mice, disrupt the integrity of the nasal mucosal epithelium, promote goblet cell hyperplasia, elevate serum levels of IL-4 and IL-6, and intensify the imbalance between Th1 and Th2 cells. Metabolomic analysis revealed that exposure to nano-SiO₂ particles in pollen-sensitized mice significantly enriched the niacin and nicotinamide metabolism pathways. Nicotinamide was demonstrated to inhibit mast cell degranulation in RBL-2H3 and BMMCs and to reduce IgE-mediated allergic reactions in the PCA model.

Conclusion: Pollen-sensitized mice exposed to nano-SiO₂ particles can aggravate allergic reactions and induce dysregulation of the metabolism characterized by niacin and nicotinamide. Nicotinamide could stabilize mast cells and may serve as a potential therapeutic strategy for allergic diseases. Further, in-depth investigations are needed.

Background: Hereditary angioedema (HAE) is a rare, life-threatening autosomal dominant disorder characterized by recurrent episodes of subcutaneous and submucosal edema. Recent years have witnessed significant advancements in HAE management globally as well as in China, including improved understanding of its pathophysiology and the development of targeted therapies. In China, since the publication of the first national consensus in 2019, accumulating clinical experience and the availability of novel therapeutic agents have created an urgent need to update diagnostic and treatment guidelines to reflect current best practices.

Summary: This updated 2024 consensus was developed through collaboration among multidisciplinary experts in allergy, otorhinolaryngology, gastroenterology, dermatology, and emergency medicine across China. It provides comprehensive, evidence-based recommendations for HAE-C1-INH management. This consensus refined diagnostic algorithms incorporating clinical presentation, quantitative/functional C1-INH assays, and complement C4 testing, with genetic sequencing reserved for cases with strong clinical suspicion but normal C1-INH levels/function. It stratified treatment approaches reflecting China's current therapeutic landscape: (1) on-demand therapy with icatibant, which is the only currently approved bradykinin B2 receptor antagonist in China; (2) short-term prophylaxis using androgens or fresh frozen plasma for procedural triggers; (3) long-term prophylaxis with lanadelumab which is the first-line monoclonal anti-kallikrein antibody available in China. Special considerations for pediatric, pregnant, and breast-feeding patients are also addressed.

Key message: As the first updated consensus since 2019, this guideline standardizes HAE management across China while addressing regional disparities in diagnostic capabilities and treatment accessibility. It emphasizes early diagnosis to prevent life-threatening laryngeal edema and promotes individualized treatment strategies tailored to China's therapeutic landscape. Future directions include emerging targeted therapies and the development of biomarkers for disease severity prediction. Implementation of these recommendations is expected to significantly reduce diagnostic delays, improve patient outcomes, and enhance quality of life for individuals with HAE in China.

Introduction: Air pollution and meteorological factors have consistently been reported to adversely affect asthma patients.

Methods: We used a linear mixed-effects model to explore the relationship between air pollution and the dynamic lung function of 58 adult asthma patients with different asthma phenotypes in Beijing, China. We conducted a follow-up panel study of these patients with repeated lung function tests every day in the morning and evening by supervised spirometry from November 2020 to December 2021. Induced sputum from these subjects was collected and analyzed for the microbiome composition and associations between microbiome and lung function indices.

Results: We found that a 10 μg/m3 increase in PM_2.5 was associated with decreases 0.79% in FEF25-75 (95% CI: 0.31-3.25), a range of decreases of 0.76%-0.83% PEF, 1.58%-1.93% for FEF25, and 1.79%-2.31% for FEF50 in the morning or evening on different lag days. Compared with the PM_2.5 effect in the fall, PM_2.5 in spring and winter had significant effects on FEV₃, FEV₆, and FVC. O₃ had significant effects on FEF25, FEF50, FEV₃, FEV₆, FVC, and FEV₁/FEV_1-predicted in summer. There is a significant reduction of lung function indices in range of 0.31% to 1.29% reduction for lung function indices associated with the summer Rh or spring Rh compared with fall Rh. PM_2.5 had a larger adverse effect on Th2 phenotype asthmatic patients than on non-Th2 phenotype asthmatic patients. For a 10 μg/m3 increase in PM_2.5, there were 0.75% (95% CI: 0.026%, 1.52%), 0.70% (95% CI: 0.010%, 1.50%), 0.75% (95% CI: 0.013%, 1.49%), and 0.37 L (95% CI: 0.062%, 0.80%) decreases on FEF50 (evening), FEF50 (morning), FEF75 (evening), and FEV₁ (morning), respectively, for the Th2 phenotype compared with those for the non-Th2 phenotype. Significant differences in the sputum microbiome composition were observed between the two inflammatory phenotypes. The linear relationships between sputum microbiome and lung function indices were observed.

Conclusion: Our study demonstrated the possibility of phenotype-environment interactions.

Introduction: Oxidative stress is associated with sleep disorders, yet the relationship between OBS - as a comprehensive measure of individual oxidative stress levels - and sleep disorders in allergic rhinitis (AR) patients remains unexplored. This study aimed to investigate whether OBS was associated with sleep disorders in AR patients.

Methods: The data presented in this study were obtained from the NHANES 2005-2006 database. Sleep disorder was determined by participants' responses to the question "Ever told by a doctor have a sleep disorder?" in the NHANES questionnaire. Univariate and multivariate logistic regression were used to analyze the association between OBS, dietary OBS, lifestyle OBS, and sleep disorders. The nonlinear relationship was further explored by RCS analysis. Mediating analysis was conducted to investigate potential mediating factors influencing the relationship between OBS/lifestyle OBS and sleep disorders.

Results: The data of 904 patients with AR were included in this study, of which 64 patients had sleep disorders and 840 patients had no sleep disorders. OBS and lifestyle OBS were associated with sleep disorders in AR patients. RCS results revealed that OBS (p for nonlinear = 0.579) and lifestyle OBS (p for nonlinear = 0.876) had a negative and linear relationship with sleep disorders. The results of the mediating analysis showed that direct HDL-C was a mediator in the relationship between OBS and sleep disorders, as well as lifestyle OBS and sleep disorders.

Conclusions: OBS and lifestyle OBS were associated with sleep disorders in AR patients. Besides, direct HDL-C was a mediator in their relationship.

Introduction: The study aimed to investigate the expression level of miR-92a-3p in combined allergic rhinitis and asthma syndrome (CARAS) and its predictive value for CARAS combined with small airway dysfunction (SAD).

Methods: This study included 85 children with allergic rhinitis and 85 children with CARAS. According to whether SAD occurred, children with CARAS were divided into 35 cases of CARAS-SAD and 50 cases of simple CARAS. The expressions of miR-92a-3p in the blood sample were detected by RT-qPCR. The pulmonary function of children with CARAS was detected by a pulmonary function tester. ROC curve was constructed to evaluate the diagnostic value of miR-92a-3p for CARAS-SAD. Logistic regression analysis was conducted to evaluate the risk factors for the occurrence of CARAS-SAD. The target genes of miR-92a-3p were predicted using the online database and GO functional annotation and KEGG pathway enrichment analysis were performed on these target genes.

Results: The expression of miR-92a-3p is increased in patients with CARAS, and the elevation in CARAS-SAD is higher than that in simple CARAS. MiR-92a-3p demonstrated excellent efficacy in differentiating CARAS-SAD from simple CARAS, with an AUC of 0.903. MiR-92a-3p, history of secondhand smoke exposure and childhood asthma control test score are independent risk factors for the occurrence of CARAS-SAD. The database predicted 403 overlapping target genes, and the pathways enriched by these target genes involved the FoxO signaling pathway and the cAMP signaling pathway.

Conclusions: Within the CARAS population, miR-92a-3p demonstrates relatively high diagnostic efficacy for CARAS-SAD, suggesting its potential as a diagnostic biomarker for CARAS-SAD. This finding indicated that miR-92a-3p has significant discriminative value for CARAS-SAD in CARAS patients.

Introduction: This study evaluated the relationship between serum fibrinogen-like protein 2 (FGL2) levels, asthma severity, lung function impairment, Th2-driven inflammation, and airway remodeling.

Methods: A comparative analysis was performed on 129 patients with asthma and 120 age- and sex-matched healthy controls. Demographic characteristics, pulmonary function indices, and serum biomarkers were assessed, and correlation analyses were conducted to examine the associations between FGL2 expression and clinical parameters.

Results: Serum FGL2 levels were significantly elevated in patients with asthma, particularly during exacerbation. FGL2 showed moderate negative correlations with forced expiratory volume in 1 second (FEV1; r = -0.333, p < 0.001) and FEV1/FVC (r = -0.321, p < 0.001) and a moderate-to-strong negative correlation with peak expiratory flow (r = -0.481, p < 0.001). Weak-to-moderate positive correlations were observed with total IgE (r = 0.255), eosinophil count (r = 0.403), and fractional exhaled nitric oxide (FeNO; r = 0.387) (all p < 0.01). Serum FGL2 levels were moderately positively correlated with Th2 cytokines, including interleukin (IL)-4 (r = 0.421), IL-5 (r = 0.277), and IL-13 (r = 0.472) (all p ≤ 0.001). Associations with airway remodeling markers were weak for matrix metalloproteinase (MMP)-2 and MMP-9, moderate for transforming growth factor-β1 (r = 0.393), and moderate to strong for hyaluronan (r = 0.481, p < 0.001). FGL2 demonstrated a good discriminatory ability for asthma, with high specificity and moderate sensitivity.

Conclusion: Elevated serum FGL2 levels correlate with asthma severity, Th2-mediated inflammation, and airway remodeling markers, supporting its potential as a complementary biomarker.

Introduction: The upstream immunological drivers of rheumatoid arthritis (RA) and their downstream proteomic effectors remain incompletely resolved. We implemented an integrated, two-layer Mendelian randomization (MR) atlas to systematically map genetically supported causal influences across immune traits and plasma proteins, nominating candidates relevant to RA pathogenesis.

Methods: In layer 1, we evaluated the causal relevance of 731 immune-cell phenotypes to RA using two-sample MR with stringent instrument filters and multiple-testing correction. In layer 2, we integrated cis-pQTLs of 4,907 plasma proteins with RA through MR and Bayesian colocalization, followed by replication in the UK Biobank, reverse MR, and transcriptomic validation in three independent RA datasets. Drug-target mapping was followed by in silico docking as a pipeline proof-of-concept rather than functional validation.

Results: Layer-1 implicated myeloid antigen-presenting were risk-enhancing, whereas adenosinergic (CD39-axis) and RAGE-axis traits showed protective directionality. Layer-2 convergently prioritized thrombin/prothrombin (F2), indicating a coagulation-inflammation coupling as a causal RA driver, coherent with known thrombo-inflammatory amplification and excess cardiovascular risk in RA. Transcriptomic validation demonstrated consistent, directionally concordant upregulation of BRD2 and MICB across all three independent RA cohorts. As a benchmark of the computational pipeline, bortezomib (BTZ) to F2 suggested structural compatibility without implying druggability (binding energy: -5.53 kcal·mol-1).

Conclusions: Genetic evidence supports an immune→coagulation causal axis in RA, nominating thrombin/F2 as a translational node and motivating a dual therapeutic rationale: suppressing procoagulant inflammation while enhancing genetically protective pathways (e.g., CD39+ and sRAGE). These findings provide a genetically anchored prioritization framework and motivate subsequent experimental and trial-proximal validation.

Introduction: In Beijing, China, the key pollen allergen components associated with spring allergic rhinitis (AR) and their potential link to pollen-food allergy syndrome (PFAS) remain incompletely characterized. This study aimed to identify the major pollen allergens that trigger AR in spring and the key pollen components that drive PFAS in Beijing.

Methods: A total of 125 patients with spring AR symptoms were enrolled during the spring pollen season in Beijing. Serum-specific IgE against pollen allergen components and food allergens was detected using ImmunoCAP and enzyme-linked immunosorbent assay. Inhibition assays were performed to verify cross-reactivity between pollen and food proteins. SPSS 26.0 software was used to analyze the correlation between pollen allergen components and PFAS-related food sensitization.

Results: Among the 125 allergic patients, the main spring pollen allergens were cypress, Fraxinus chinensis, plane tree, willow, Populus, white birch and elm, while Artemisia sieversiana, sunflower, and goosefoot were the main autumn pollen allergens. The highest positive rate of Cup a 1 (60.9%) was observed for cypress, the highest positive rate of Art an 2 (64.8%) for Artemisia annua, and the highest positive rate of Che a 2 (80%) for goosefoot. Spearman's correlation analysis indicated that Art an 4 cross-reacted with peach (r = 0.766, p < 0.0001), and Che a 2 cross-reacted with peach (r = 0.914, p < 0.001), which were confirmed by inhibition assay.

Conclusion: Spring AR patients should be alert for the possible cross-reactivity to some food and autumn pollen allergy. We found Art an 4 profilin sensitization has much impact on peach Pru p 4 and goosefoot pollen Che a 2 positivity, highlighting the need to detect both spring and autumn pollen components for early PFAS risk screening in spring.

Introduction: Allergic rhinitis (AR) significantly impairs quality of life. Although baicalin is known for its anti-inflammatory properties, its therapeutic potential via localized nasal delivery remains unexplored. This study evaluated the efficacy and potential mechanisms of baicalin nasal irrigation in an AR mouse model.

Methods: Ovalbumin (OVA)-induced BALB/c mice (n = 17 per group) were randomized into six groups: control, AR model, baicalin, loratadine, combination of baicalin and loratadine, and excipient. Nasal symptom scores were recorded pre- and post-treatment. Serum and nasal lavage fluid (NALF) levels of total immunoglobulin E (IgE), OVA-specific IgE, OVA-specific IgG1, and eosinophil cationic protein (ECP) were quantified by ELISA. Nasal mucosal pathology was assessed through hematoxylin and eosin staining (eosinophil counts) and MUC5AC immunofluorescence (goblet cell hyperplasia). Tight junction proteins (ZO-1, occludin) were visualized via immunofluorescence. Transcriptomic profiling of nasal tissues identified baicalin-modulated pathways, with key chemokines validated by immunohistochemistry.

Results: Baicalin significantly improved nasal symptom scores, reduced eosinophil and goblet cell infiltration, and decreased total IgE, OVA-specific IgE, OVA-specific IgG1, and ECP in serum and NALF. It was more effective than loratadine in reducing tissue eosinophils and suppressing local inflammatory markers. Baicalin also restored mucosal barrier proteins ZO-1 and occludin. Transcriptomic analysis revealed modulation of chemokines (CCL6, CCL8, and CCL24) involved in eosinophil chemotaxis, a finding corroborated by protein-protein interaction analysis and immunohistochemistry.

Conclusion: Baicalin nasal irrigation inhibits eosinophil chemotaxis and alleviates AR symptoms, highlighting its potential as a novel local therapeutic strategy for AR.

Introduction: Sepsis, a severe infectious disease, is characterized by high mortality and significant therapeutic challenges. This study aims to systematically review the impact of immunomodulatory therapy on sepsis-related mortality and create an evidence-based foundation for sepsis treatment.

Methods: A systematic search was conducted in multiple databases including CNKI, VIP, Wanfang Data, and PubMed, with a cutoff date of November 6, 2024. The Cochrane Risk of Bias 2.0 tool was employed to evaluate the risk of bias for randomized controlled trials (RCTs), and the Newcastle-Ottawa Scale was used for non-RCTs (NRCTs). Data analyses were conducted via the R package meta, with the relative risk (RR) and 95% CI as effect sizes. Heterogeneity was evaluated using the Cochran's Q test and I2 statistic, and publication bias was judged by a funnel plot.

Results: A total of 1,783 articles were retrieved, and 21 articles (including 22 comparison groups) were finally included after screening, involving 19 RCTs and 2 NRCTs with a total of 5,276 patients. Meta-analysis results indicated that immunomodulatory therapy could reduce the risk of death in patients with sepsis (RR = 0.87, 95% CI: 0.81-0.93, I2 = 44%, p = 0.01). Subgroup analysis revealed that the overall heterogeneity mainly came from immunoglobulin G therapy (I2 = 63%), while the effects of afelimomab, methylprednisolone, Xuebijing, α1-thymosin (Tα1), and ulinastatin + Tα1 therapies were highly consistent with zero heterogeneity.

Conclusion: Immunomodulatory therapy can reduce the risk of death in patients with sepsis, but there is moderate heterogeneity, and its efficacy may be affected by factors such as the type of specific immunomodulatory therapy.