Journal of Investigational Allergology and Clinical Immunology最新文献

Background and objectives: Occupational asthma (OA) is an increasingly relevant respiratory disease in modern workplaces. Epidemiological evidence highlights its considerable prevalence among the global working population, with recent increases following an initial decline in the early 21st century. To critically review the pathophysiological mechanisms, risk factors, clinical presentations, and emerging challenges associated with OA, focusing on novel exposures, biomarker development, and translation of scientific findings into preventive and clinical practice.

Methods: A literature review was conducted through a bibliographic search in PubMed (MEDLINE) and Web of Science. Articles were selected and analyzed using the Rayyan collaborative platform. Empirical studies on prevalence, risk factors, diagnosis, and management of OA were included.

Results: OA is primarily categorized as sensitizer- or irritant-induced, each exhibiting unique molecular pathways and clinical courses. Transcriptomic research has identified specific microRNA profiles as innovative biomarkers with significant diagnostic capacity. Studies document risks in traditionally non-high-risk sectors, such as offices and educational environments. Factors such as work chronobiology (night shifts), sex, and socioeconomic status influence the development and prognosis of OA, potentially leading to loss of productivity and employment.

Conclusion: OA is a significant challenge in occupational health, with complex epidemiological patterns. While advances in molecular characterization and identification of emerging risk factors have improved our understanding of the condition, diagnostic and management challenges persist. Future research should focus on developing specific biomarkers and accessible diagnostic tools for primary care, along with evidence-based preventive strategies for emerging labor sectors.

Dupilumab has proven effective in the treatment of eosinophilic esophagitis (EoE) in randomized controlled trials. Its efficacy in other, less common and generally more severe eosinophilic gastrointestinal disorders (EGIDs) is scientifically plausible, although it has not been studied to date. Our objective was to describe published and our experience on the empirical use of dupilumab in patients affected by EGIDs with extraesophageal involvement. We retrospectively analyzed the medical charts of children diagnosed with extraesophageal EGIDs treated with dupilumab at our tertiary medical center. The Medline, Embase, and Cochrane databases were searched up to January 2025 for articles describing the use of dupilumab in patients with diagnosed or suspected extraesophageal EGID. Our cohort included 8 patients with a clinical and histological diagnosis of EGID and extraesophageal involvement. All of them had recurrent gastrointestinal symptoms refractory to standard treatments. Three patients had growth retardation. In all patients, symptoms and macroscopic and histological abnormalities, including eosinophilic infiltration, quickly improved after initiation of dupilumab. The systematic review identified 11 case reports (n=29 patients) of pediatric and adult patients with extraesophageal EGIDs treated with dupilumab. All 11 reports described significant clinical and histological improvement following therapy. Clinical experience suggests that dupilumab is effective in treating pediatric EGIDs with extraesophageal features. Given the rarity and high morbidity of these disorders, dupilumab could be considered a reasonable option while waiting for high-quality evidence from ongoing randomized controlled trials.

Background and objectives: Kimura disease (KD) is a rare chronic inflammatory disorder characterized by type 2 immune dysregulation. Conventional treatments have shown limited efficacy, whereas biologics targeting type 2 cytokines show therapeutic potential. This study aimed to evaluate the efficacy and safety of dupilumab, a monoclonal antibody targeting interleukin (IL) 4 and IL-13, in the treatment of KD.

Methods: A retrospective case series comprising 8 patients with KD was studied at the Allergy Clinic of the Second Affiliated Hospital of Zhejiang University School of Medicine from October 2021 to June 2024. Patients received dupilumab according to the approved regimen for atopic dermatitis, starting with a 600-mg loading dose followed by 300 mg every 2 weeks. The dosage was gradually tapered based on the clinical response to 300 mg monthly, then every 6 weeks, and finally every 2 months until the drug was eventually discontinued. Clinical outcomes, including mass reduction, serum IgE levels, eosinophil counts, and allergic comorbidities, were assessed.

Results: Mass volume was reduced considerably in all 8 patients, with 7 achieving complete remission and 1 attaining partial remission. Both serum IgE levels and eosinophil counts decreased markedly. No clinically significant adverse drug reactions were observed. Several patients remained in remission after discontinuation, with follow-up extending up to 1 year.

Conclusion: Dupilumab showed rapid and sustained efficacy in KD, suggesting its potential as a disease-modifying and corticosteroidsparing treatment option. Further controlled studies are warranted to validate these findings.

Background and objectives: Provocation tests with contrast media are increasingly necessary to complete an allergy work-up. However, they are not standardized. We aimed to evaluate a rapid provocation test in patients with a history of anaphylaxis. Our secondary objectives included phenotyping the study population and proposing a predictive methodology for allergy test outcomes.

Methods: We performed an allergy study using iohexol, iodixanol, ioversol, and iobitridol in patients ≥18 years of age with previous hypersensitivity reactions to iodinated contrast media. A rapid provocation test (100 cc administered in 12 minutes) was performed using a noninvolved iodinated contrast medium that had yielded negative skin test results. The statistical analysis comprised binary logistic regression and cluster analysis.

Results: A total of 130 patients were enrolled. Ninety-six patients (74%) developed cutaneous symptoms exclusively, while 17 patients (13%) experienced anaphylaxis. Nine patients (7%) had positive skin test results, and 20 of 141 provocation tests performed were positive. All patients developed mild cutaneous symptoms, including those with a history of anaphylaxis. A safe alternative contrast medium was recommended to 122 patients (94%), with good tolerance in 50 patients in a new radiological examination. We identified 3 patient phenotypes, each associated with a different risk of a positive drug provocation test result. A predictive model for allergy test outcomes was developed, although its statistical predictive capacity was low.

Conclusion: confirmed the efficacy and safety of a protocol including rapid provocation tests in patients with hypersensitivity reactions to iodinated contrast media of varying severity. Three patient clusters were identified, each showing a different risk level for a positive provocation test result.

Background: Asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) are both type 2 (T2) inflammatory diseases that frequently co-occur and are interconnected through shared immunological pathways. The anti-IL-5 monoclonal antibody mepolizumab has shown efficacy in reducing eosinophilic inflammation and improving clinical outcomes. However, the molecular mechanisms underlying response to treatment, particularly at the transcriptomic level, remain underexplored. We aimed to investigate peripheral blood transcriptomic changes and identify potential biomarkers associated with dual super-response to mepolizumab in patients with severe asthma and CRSwNP.

Methods: The study population comprised 29 participants (19 patients with severe asthma and CRSwNP and 10 healthy controls). Whole blood RNA sequencing was performed before and after treatment with mepolizumab in 6 patients, followed by validation of candidate genes using qPCR. Clinical responses were assessed using the FEOS score (FEV1, exacerbations, oral corticosteroids, symptoms) and lung function measurements, and the 22-item Sino-Nasal Outcome Test (SNOT-22) score.

Results: Mepolizumab significantly improved clinical parameters, including exacerbation rates, asthma control, and the SNOT-22 score. Transcriptomic analysis identified 156 differentially expressed genes after treatment with mepolizumab, significantly enriching immune and inflammatory pathways. Twelve candidate genes were studied. Three of these genes (PNPLA1, C3AR1, and RGS1) were validated as potential predictors of super-response to treatment of asthma and CRSwNP. Baseline expression levels of RGS1 were associated with dual super-response in asthma and CRSwNP.

Conclusion: This study provides new insights into transcriptomic changes following mepolizumab treatment and highlights RGS1 as a potential biomarker for predicting dual super-response in asthma and CRSwNP. Our findings contribute to precision medicine approaches and support the identification of optimal candidates for anti-IL-5 therapy.

Background and objectives: House dust mite (HDM) allergy is a leading cause of allergic rhinoconjunctivitis and asthma. Among the major HDM allergens, Der p 23 has been recognized as clinically relevant. However, allergen immunotherapy (AIT) extracts often lack defined amounts of Der p 23, which may compromise treatment in patients sensitized exclusively to this component. Objective: To determine the prevalence of monosensitization to Der p 23 among HDM-allergic patients and to assess the capacity of commercial HDM skin prick test (SPT) extracts to inhibit IgE binding.

Methods: A retrospective analysis on 1700 HDM-allergic patients was carried out between 2019 and 2023. Specific IgE to Der p 1, 2, and 23 was measured using ImmunoCAP. Monosensitization to Der p 23 was defined as sIgE >0.35 kUA/L to Der p 23 and <0.10 kUA/L to Der p 1 and 2. Additional molecular profiling (ALEX microarray) was performed to confirm exclusive sensitization. sIgE inhibition assays were used to evaluate 5 commercial HDM extracts.

Results: Almost two-thirds of patients (62.3%) were sensitized to Der p 23, and 3.47% (n=59) were monosensitized. Of these, 72.7% (16/22) were confirmed by ALEX. SPT extracts inhibited IgE binding in between 42% and 77% of cases depending on the manufacturer.

Conclusions: The findings indicate that monosensitization to Der p 23, though relatively infrequent, affects a clinically relevant subset of patients. Commercial extracts vary in their ability to inhibit sIgE to Der p 23, underscoring the need for improved extract formulations and further research into the efficacy of AIT in this subgroup.

Background: An environmental exposure chamber (EEC) is a health facility that enables allergic symptoms to be induced in a controlled manner in persons sensitized to a dispersed allergen. We performed a study at our institution to technically and clinically validate an EEC in patients allergic to grass pollen.

Methods: We developed a new EEC inside a clean room (ISO-8 class) measuring 15.6 m². During the technical validation, the patient's exposure conditions were simulated by ensuring homogeneous distribution of the allergen with a particle disperser and monitoring both particle and pollen grain concentrations. Temperature, pressure, and humidity were also registered. A total of 31 volunteers were exposed to Phleum pratense pollen in the EEC. Of these, 25 were allergic (cases), with symptoms of rhinoconjunctivitis with or without asthma, and 6 were not (controls). One control and 2 cases were exposed twice to check reproducibility, generating a total of 34 challenges. The test was stopped once the positivity criterion was reached or the patient completed 90 minutes in the EEC.

Results: Both the stability of particle concentrations and approximation to the pollen sample concentration were guaranteed. All challenges with controls were negative. Among the cases, 15% of challenges were negative and 85% were positive. No severe or late reactions were observed. Volunteers exposed twice to the same pollen had the same result in both challenges.

Conclusions: Our EEC proved to be a specific, safe, and reproducible tool for the diagnosis of grass pollen allergy.

Background: Hereditary angioedema (HAE) is a rare and potentially life-threatening disease, and diagnosis is often missed or delayed. We aimed to identify noninvasive urinary protein biomarkers and to evaluate their potential roles in diagnosis and evaluation of disease severity.

Methods: Using data-independent acquisition (DIA)-based urinary proteomics, we identified proteins that were differentially expressed between patients with HAE and healthy control (HC) groups. Then, the parallel reaction monitoring (PRM)-targeted proteomics method was used to validate promising biomarker candidates in other HAE patients and HCs. Furthermore, enzyme-linked immunosorbent assay (ELISA) was conducted to verify levels of several key proteins in HAE, histamine-mediated angioedema, and HCs.

Results: Differential expression between HAE patients and HCs was observed in 269 of the 2562 urinary proteins identified. In the biofunction analysis, these differentially expressed proteins were significantly enriched in leukocyte migration, adhesion of immune cells, endothelial cell development, permeability of the vascular system, and death of immune cells. Moreover, a biomarker panel (C1 esterase inhibitor, pro-epidermal growth factor, and kininogen-1) was validated in 2 independent clinical cohorts with area under the curve values of 0.910 and 0.949 for a diagnosis of HAE. Additionally, the urinary clusterin level was found to be significantly correlated with HAE severity scores (R=-0.758, P<.01).

Conclusions: This study describes the first application of a DIA-PRM-ELISA workflow to identify noninvasive urine biomarkers of HAE. The results will contribute to our understanding of the pathogenesis of HAE and may also provide a potential alternative method for diagnosis and evaluation of disease severity.