International Archives of Allergy and Immunology最新文献

Introduction: Silica exposure is a significant environmental hazard linked to lung inflammation and fibrosis. Despite general protective measures, there remains a critical need for pharmacological interventions targeting the molecular mechanisms of silica-induced lung injury and fibrosis.

Methods: In silico reanalysis of publicly available transcriptomic datasets (GSE250537, GSE142446) from silica-exposed Fischer-344 rats was conducted to investigate molecular pathways and therapeutic targets. Rats were exposed to crystalline silica via inhalation, and lung/blood transcriptomes were analyzed at 1 day, 3, 6, and 9 months post-exposure. Differential expression, gene set enrichment analysis (GSEA), protein-protein interaction (PPI) clustering, and drug-gene matching (Open TG-GATEs) were performed, followed by in vivo validation of simvastatin in a murine silica fibrosis model.

Results: GSEA revealed activation of fibro-inflammatory and aging pathways in lung tissue, including TGF-beta, NOD-like receptor protein 3, and TNF-α signaling, with limited effects in blood. Differential expression identified 12 fibrotic markers consistently upregulated in lung tissue, such as Cxcl6, Mmp12, and S100a9, implicated in inflammation, tissue remodeling, and fibrosis. Temporal analysis showed prolonged upregulation up to 9 months post-exposure. Protein-protein interaction networks highlighted clusters related to chemokine signaling, tissue remodeling, and matrix metalloproteinases. Using the Open TG-GATEs database, 179 pharmacological agents were identified, with 37 targeting five or more fibrotic genes. Notable candidates included non-steroidal anti-inflammatory drugs, captopril, and simvastatin. In vivo validation in a silica-induced murine fibrosis model showed that simvastatin significantly reduced key fibro-inflammatory genes and attenuated increases in fibrotic markers in lung tissue.

Conclusion: These findings provide insights into silica immunopathology and potential drug repurposing strategies; however, further studies are warranted to elucidate mechanisms and evaluate therapeutic efficacy in clinical settings.

Introduction: Allergic rhinitis (AR) is a prevalent health concern. In Europe, 20-40% of the population is affected. Diagnostic methods include skin tests, measurement of serum immunoglobulin E (IgE), nasal smear for eosinophils, and inhalation provocation tests. The introduction of the nasal allergy test has simplified allergen testing for the direct determination of specific IgE on the nasal mucosa.

Methods: A prospective study conducted from 2010 to 2012 included 102 participants diagnosed with AR and 60 control participants without persistent AR, based on medical history and physical examination. Participants from both groups underwent a nasal test using prepared inhalant allergy panels. Specific IgE was tested using the ELISA processor Hytec 288. The aim of the study was to interpret diagnostic accuracy measures for each allergen panel.

Results: The nasal allergy test demonstrated sensitivity above 75%, and specificity approaching 90%. The positive predictive value was 91.25%, while the negative predictive value was 71%. The positive likelihood ratio (LR) ranged from 3.75 to 34.59, indicating that a positive result was 10.23 times more likely in patients than in controls. A negative LR was 0.25, suggesting that participants in the control group were four times more likely to yield a negative result than allergic individuals.

Conclusion: The nasal allergy test is recommended due to its simplicity, minimal risk profile compared to conventional tests, and high diagnostic reliability.

Introduction: Baked egg (BE) is generally well tolerated by children with egg allergy, and heated egg yolk (EY) is considered less allergenic than egg white (EW). Although these findings suggest that both BE and EY may be safer options for reintroduction, no studies have directly compared their safety with each other or with heated EW. This study aimed to compare the safety of oral food challenge (OFC) for reintroducing BE, EY, and EW in children with egg allergy.

Methods: We retrospectively analyzed data from patients who underwent OFCs with BE, EY, or EW at the Department of Allergy, Kanagawa Children's Medical Center, between 2014 and 2024. Only patients with a history of acute IgE-mediated allergic reactions (within 2 h of egg ingestion), an EW-specific IgE level ≥0.35 UA/mL, and strict avoidance of egg protein at the time of OFC were eligible for inclusion.

Results: Ninety-seven children under 3 years of age were enrolled (BE group, n = 47; EY group, n = 23; EW group, n = 27). The OFC positive rate was significantly lower in the BE group (0%) compared to the EY (17.4%) and EW (22.2%) groups (p = 0.0011). Although mild skin or gastrointestinal reactions were observed in the EY group, 2 patients in the EW group experienced respiratory reactions. No patient required adrenaline administration.

Conclusion: OFC with a small amount of BE demonstrated a low positivity rate and could be safely performed even in children with a history of egg-induced reactions.

Introduction: The aim of the study was to assess the frequency and clinical-immunologic characteristics of immune-related comorbidities in children with genetically confirmed familial Mediterranean fever.

Methods: This cohort study included 132 pediatric patients with a genetically confirmed diagnosis of FMF, followed at a tertiary care center. Patients were stratified into two groups based on the presence or absence of immune-related comorbidities. Clinical manifestations, laboratory parameters, MEFV mutation profiles, and treatment modalities were comparatively analyzed. Statistical significance was set at p < 0.05.

Results: Immune-related comorbidities were identified in 37.8% of patients, including 12 with defined inborn errors of immunities. These patients more frequently presented with atypical symptoms such as diarrhea, rash, aphthous stomatitis, and appetite loss, while classical symptoms like fever and abdominal pain were less common. Tonsillitis was significantly more frequent in the non-comorbidity group (p = 0.046). Strong antinuclear antibody positivity and immunoglobulin deficiencies were significantly associated with the comorbidity group. Although MEFV mutation patterns did not differ between groups, intravenous immunoglobulin therapy was administered exclusively in patients with immune-related comorbidities (p < 0.001).

Conclusion: A notable subset of pediatric familial Mediterranean fever patients demonstrates immune dysregulation extending beyond innate autoinflammation. These findings underscore the importance of immunologic assessment in patients with atypical features or inadequate response to colchicine. Early identification and appropriate immunomodulatory interventions may improve clinical outcomes in this distinct subgroup.

Introduction: This study aimed to identify systemic lupus erythematosus (SLE)-associated plasma proteins, particularly those linked to M1 macrophage activation, using an integrative multi-omics approach.

Methods: We performed two-sample Mendelian randomization (MR) analysis using protein quantitative trait loci data and SLE genome-wide association study (GWAS) data to assess associations between genetically predicted plasma protein levels and SLE risk. Validation was conducted using FinnGen SLE data, supplemented by single-cell RNA sequencing (scRNA-seq), Bayesian colocalization, in vitro M1 macrophage experiments of primary human peripheral blood monocytes and THP-1 cells, SLE patients' plasma sample validation, and molecular dynamics simulations.

Results: By integrating MR analysis, scRNA-seq analysis, Bayesian colocalization analysis, and in vitro M1 macrophage activation experiments, this study identified ATG4B, NLRP1, and PDCD4 as important causal plasma proteins associated with M1 macrophage activation. The plasma samples of patients with SLE validated the protein expression of ATG4B and NLRP1. Phenome-wide association studies (PheWASs) found no significant links between these proteins and other complex traits. Drug target analysis, molecular docking, and molecular dynamics simulations supported the strong binding affinities and stability for the target proteins ATG4B and NLRP1 with their candidate drugs.

Conclusion: Our multi-omics and molecular dynamics simulation identified ATG4B and NLRP1 as potential SLE biomarkers and therapeutic targets, with implications for M1 macrophage-driven pathogenesis.

Background: Allergic airway inflammation, including allergic rhinitis and asthma, is a disease characterized by immunoglobulin E-mediated type I hypersensitivity reactions, with its pathophysiological features characterized by infiltration and proliferation of inflammatory cells in the airway mucosal epithelial cells. The complexity and heterogeneity of this inflammatory response, as well as the limitations of sampling from patients with allergic airway inflammation, have made animal models play a crucial role in studying the pathophysiological molecular pathways and treatment methods of allergic airway inflammation.

Summary: Among the many animal models studied for allergic airway inflammation, mouse models are widely used for their diversity of genetic backgrounds, ease of experimental manipulation, and relevance to human diseases. When constructing and evaluating mouse models, many factors must be considered, including the selection of allergens, the selection of mouse species that are sensitive to allergens and have significant immune responses, the selection and feasibility of reagents and gene targets related to allergic airway inflammation, and the correlation with human natural diseases, i.e., whether the mouse model can be used to answer clinical questions about allergic airway inflammation, etc. Key Message: This review aimed to summarize the latest advances in mouse models used for allergic airway inflammation research, so as to provide further insights into the pathophysiology and treatment of allergic airway inflammation.

Introduction: Between 10% and 20% of all prosthesis patients experience implant-related complications within 1-2 years following surgery. Hypersensitivity to components within the prosthesis is a possible cause of these complications.

Methods: This study aimed to investigate the characteristics of prosthesis-related hypersensitivity (PRH) and identify possible associated risk factors. A retrospective, monocentric study was conducted at the University Hospital Zurich.

Results: A total of 225 patients who underwent patch testing for suspected PRH between 2011 and 2021 were included. The mean age was 72 years; 34% were male and 65% were female. Knee pain was the most commonly reported symptom (85%), followed by eczematous skin lesions and joint instability (each around 20%), as well as redness or swelling (13-16%). In 67% of the patients undergoing patch testing, an allergy was diagnosed. Nickel was the most frequently identified allergen (31.5%), followed by vanadium chloride (13.7%) and gentamycin, an antibiotic, often added to bone cement. 60% of the PRH patients had a previously known contact allergy - 25.7% to metals and 34.6% to other substances. Among the metals, nickel was the most prevalent (19.5%), followed by silver (3.1%). This prevalence was significantly higher than in patients without a metal allergy diagnosis. No significant differences were observed between the groups regarding overall or individual atopic comorbidities (present in approximately 40% of patients).

Conclusion: A history of contact allergy may be an indicator of PRH. In contrast, clinical presentation and the consideration of atopic or non-atopic comorbidities in prosthesis patients with suspected PRH do not appear to provide helpful diagnostic clues. Based on our findings, PRH may represent an underestimated cause of postoperative complaints.

Introduction: Platelet activation contributes to airway inflammation. Mean platelet volume (MPV) has been proposed as a marker of systemic inflammation. However, its association with asthma control is unclear. This study aimed to explore the association between asthma control status and MPV in children with asthma and to determine whether MPV and C-reactive protein (CRP) levels are markers of systemic inflammation across varying disease activities, including during exacerbations.

Methods: In this cross-sectional study, 414 children (331 with asthma, 83 controls) were analysed. Asthma diagnosis and control status were determined according to the GINA guidelines. Peripheral blood indices, including MPV, CRP, and spirometric parameters, were compared across the following groups: controlled asthma, uncontrolled asthma, asthma exacerbation, and controls. Children with exacerbation were re-evaluated 3 months after discharge.

Results: The MPV was significantly lower in children with asthma exacerbation and uncontrolled asthma than in those with controlled asthma or healthy controls. MPV exhibited a strong inverse correlation with CRP levels across all asthma subgroups (r = -0.361 to -0.664, p < 0.001). The CRP levels and white blood cell (WBC) counts increased during exacerbations and decreased upon clinical recovery, whereas the MPVs increased post-exacerbation. No significant correlations were observed in the healthy controls.

Conclusion: MPV decreases in children during asthma exacerbations and uncontrolled disease, inversely correlating with CRP levels, and normalizes with clinical improvement. These findings support MPV as a non-invasive biomarker of systemic inflammation and asthma control in paediatric patients. The distinct activation profile of platelets in inflammation may provide novel insights into disease monitoring and therapeutic targeting.

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.