Allergy最新文献

{"title":"Dupilumab and Blood Eosinophilia: A Disease-Specific Phenomenon?","authors":"Andrea Portacci, Remo Poto, Gilda Varricchi, Giovanna Elisiana Carpagnano","doi":"10.1111/all.16610","DOIUrl":"10.1111/all.16610","url":null,"abstract":"<p>Dupilumab, a fully human monoclonal antibody that targets the interleukin (IL)-4 receptor alpha subunit (IL-4Rα) blocking IL-4 and IL-13 signaling, has revolutionized the treatment landscape for several type 2 (T2) inflammatory diseases, including severe asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), atopic dermatitis (AD), and eosinophilic esophagitis (EoE) [<span>1</span>]. Despite its therapeutic efficacy, the occurrence of transient blood eosinophilia during dupilumab treatment across different T2 diseases remains poorly understood. This phenomenon is generally not associated with clinical symptoms or impact on efficacy, occurs in the first few weeks, and returns to baseline or lower by the end of the treatment period. As reported by Wechsler et al. in a post hoc analysis of dupilumab trials involving patients with severe asthma, CRSwNP, and AD, transient blood eosinophilia occurs in a subset of individuals. This finding suggests that transient blood eosinophilia may be linked to a specific endotype of T2 inflammation that predisposes individuals to this response [<span>2</span>]. Nevertheless, while several molecular mechanisms have been proposed to explain the presence of blood eosinophilia during the blockage of the IL-4/IL-13 axis in patients with severe asthma, CRSwNP, and AD, the absence of this phenomenon in chronic obstructive pulmonary disease (COPD) and EoE remains elusive. This discrepancy raises key questions about whether blood eosinophilia is primarily driven by dupilumab mechanisms of action or by underlying disease-specific immune pathways. Moreover, understanding these differences could have practical implications for clinical management, particularly in terms of monitoring adverse effects and tailoring treatment strategies.</p><p>The rise in blood eosinophils observed during dupilumab treatment has been attributed to multiple mechanisms, highlighting the role of cytokine dynamics and eosinophil trafficking. One hypothesis suggests that dupilumab-induced eosinophilia results from altered vascular cell adhesion molecule-1 (VCAM-1) expression, a key molecule mediating eosinophil adhesion to endothelial cells. Blocking IL-4/IL-13 reduces VCAM-1 expression, leading to decreased eosinophil migration from circulation into tissues, thereby increasing eosinophil counts in the blood [<span>3, 4</span>]. However, the expression of VCAM-1 differs across diseases. Patients with COPD could exhibit a higher expression of VCAM-1, especially those with increased cardiovascular risk [<span>5</span>]. This augmented VCAM-1 expression could facilitate eosinophil retention within tissues, thereby preventing their accumulation in the bloodstream despite IL-4/IL-13 axis blockade (Figure 1). Similarly, in patients with EoE, VCAM-1 is highly expressed on the esophageal vascular endothelium, eosinophils, and mast cells [<span>6</span>]. In EoE, VCAM-1 expression is primarily driven by IL-18, a cytokine involved in some aspects of bo","PeriodicalId":122,"journal":{"name":"Allergy","volume":"80 6","pages":"1811-1814"},"PeriodicalIF":12.6,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.16610","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144256837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impact of Rhinovirus, Syncytial Respiratory Virus and Helminth Infection on the Risk of New-Onset Asthma and Other Allergic Conditions—A Systematic Review for the EAACI Guidelines on Environmental Science for Allergic Diseases and Asthma","authors":"Ioana Agache,&nbsp;Josefina Salazar,&nbsp;Yesenia Rodriguez-Tanta,&nbsp;Fiorella Karina Fernandez Saenz,&nbsp;Tari Haahtela,&nbsp;Claudia Traidl-Hoffmann,&nbsp;Athanasios Damialis,&nbsp;de las Letizia Vecillas,&nbsp;Mattia Giovannini,&nbsp;Kari C. Nadeau,&nbsp;Isabella Pali-Schöll,&nbsp;Oscar Palomares,&nbsp;Harald Renz,&nbsp;Jurgen Schwarze,&nbsp;Bernardo Sousa Pinto,&nbsp;Marilyn Urrutia-Pereira,&nbsp;Carina Venter,&nbsp;Donata Vercelli,&nbsp;Tonia Winders,&nbsp;Ivan Sola-Arnau,&nbsp;Pablo Alonso-Coello,&nbsp;Carlos Canelo-Aybar,&nbsp;Marek Jutel,&nbsp;Cezmi A. Akdis","doi":"10.1111/all.16611","DOIUrl":"10.1111/all.16611","url":null,"abstract":"<p>This systematic review evaluated the association between lower respiratory tract infections (LRTI) in infancy with respiratory syncytial virus (RSV), rhinovirus (RV) or infestation with helminths and the risk of developing asthma and allergic diseases. The risk of bias was assessed with ROBINS-E, and the certainty of evidence (CoE) with GRADE. Meta-analysis applied a random-effects model. RSV LRTI is likely associated with an increased risk of developing asthma by age 7 (OR 3.02, 95% CI 2.23–4.09; <i>I</i>² = 98%; moderate CoE). The impact on wheezing, atopic dermatitis (AD), and allergic rhinitis is uncertain. RV LRTI may be associated with increased risk of developing asthma (OR 8.40, 95% CI 2.56–27.55; <i>I</i>² = 43%; low CoE). The impact on wheezing and AD is uncertain. <i>Trichuris trichiura</i> infestation might be associated with reduced risk of new-onset wheezing (OR 0.57, 95% CI 0.35–0.94; very low CoE) or AD (HR: 0.35, 95% CI 0.18–0.67; very low CoE). The association between <i>Ascaris lumbricoides</i> and hookworm infestation and the risk of developing asthma or AD is uncertain. Infestation with any helminths might be associated with reduced risk of new-onset asthma by age 5 (OR: 0.60, 95% CI 0.38–0.95; very low CoE) and wheezing (OR 0.70, 95% CI 0.51–0.95; very low CoE). More high-quality studies are needed to confirm these findings.</p>","PeriodicalId":122,"journal":{"name":"Allergy","volume":"80 7","pages":"1878-1898"},"PeriodicalIF":12.6,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.16611","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Keratinocyte-Derived Glucocorticoids Maintain Immune Balance During Transient Skin Barrier Perturbation.","authors":"Truong San Phan, Rebekka Lambrecht, Verena M Merk, Alice Wiedmann, Pascale Zwicky, Burkhard Becher, Thomas Brunner","doi":"10.1111/all.16613","DOIUrl":"https://doi.org/10.1111/all.16613","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":" ","pages":""},"PeriodicalIF":12.6,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144223807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetically Determined Inflammation-Related Proteins in Asthma and Type-2 Signatures","authors":"Natalia Hernandez-Pacheco,&nbsp;Sophia Björkander,&nbsp;Simon Kebede Merid,&nbsp;Maura Kere,&nbsp;Ashish Kumar,&nbsp;Susanna Klevebro,&nbsp;Ida Mogensen,&nbsp;Sandra Ekström,&nbsp;Christer Janson,&nbsp;Lena Palmberg,&nbsp;Marianne van Hage,&nbsp;Anders Mälarstig,&nbsp;Anne-Sophie Merritt,&nbsp;Göran Pershagen,&nbsp;Anna Bergström,&nbsp;Inger Kull,&nbsp;Jochen M. Schwenk,&nbsp;Erik Melén","doi":"10.1111/all.16608","DOIUrl":"10.1111/all.16608","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Protein quantitative trait loci (pQTLs) remain underexplored in asthma but might provide valuable insights into the underlying molecular mechanisms. This study aimed to investigate associations between genetic variation and inflammation-related plasma proteins and to assess differences in the levels of genetically determined proteins in subjects with signatures of type-2 inflammation and/or asthma.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A pQTL mapping of 92 inflammation-related plasma proteins was conducted in young adults from the Swedish BAMSE cohort (<i>n</i> = 1538). Replication of sentinel pQTLs was attempted, and the overlap and colocalization of pQTLs with expression quantitative trait loci (eQTLs) were investigated using publicly available data. Proteins with significant pQTLs were tested for association with type-2 signatures defined as high levels of fractional exhaled nitric oxide, blood eosinophils, and/or sensitization to airborne allergens in subjects with or without asthma in BAMSE.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Forty-five sentinel pQTLs (33 <i>cis</i>, 12 <i>trans</i>) for 39 inflammation-related proteins were identified (<i>p</i> ≤ 7.14 × 10⁻¹¹), and a high proportion of these were validated in independent populations. A high likelihood for colocalization of <i>cis</i>-pQTLs and <i>cis</i>-eQTLs was observed for 19 proteins in different tissues. Six of the 39 circulating proteins with significant pQTLs were associated with type-2 signatures and/or asthma, and matrix metalloproteinase-10 (MMP-10) showed the most significant associations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings underscore the existence of a genetic component influencing the plasma levels of proteins involved in inflammatory processes, including MMP-10, which is suggested to have a role in high type-2 inflammation in asthma subjects.</p>\u0000 </section>\u0000 </div>","PeriodicalId":122,"journal":{"name":"Allergy","volume":"80 6","pages":"1702-1714"},"PeriodicalIF":12.6,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.16608","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene-Environment Interaction Affects Risk of Atopic Eczema: Population and In Vitro Studies.","authors":"Marie Standl, Ashley Budu-Aggrey, Luke J Johnston, Martina S Elias, S Hasan Arshad, Peter Bager, Veronique Bataille, Helena Blakeway, Klaus Bønnelykke, Dorret Boomsma, Ben M Brumpton, Mariona Bustamante Pineda, Archie Campbell, John A Curtin, Anders Eliasen, João P S Fadista, Bjarke Feenstra, Trine Gerner, Carolina Medina-Gomez, Sarah Grosche, Kristine B Gutzkow, Anne-Sofie Halling, Caroline Hayward, John Henderson, Esther Herrera-Luis, John W Holloway, Joukejan Hottenga, Jonathan O'B Hourihane, Chen Hu, Kristian Hveem, Amaia Irizar, Benedicte Jacquemi, Leon Jessen, Sara Kress, Ramesh J Kurukulaaratchy, Susanne Lau, Sabrina Llop, Mari Løset, Ingo Marenholz, Dan Mason, Daniel L McCartney, Mads Melbye, Erik Melén, Camelia Minica, Clare S Murray, Tamar Nijsten, Luba M Pardo, Suzanne Pasmans, Craig E Pennell, Maria R Rinnov, Gillian Santorelli, Tamara Schikowski, Darina Sheehan, Angela Simpson, Cilla Söderhäll, Laurent F Thomas, Jacob P Thyssen, Maties Torrent, Toos van Beijsterveldt, Alessia Visconti, Judith M Vonk, Carol A Wang, Cheng-Jian Xu, Ali H Ziyab, Adnan Custovic, Paola Di Meglio, Liesbeth Duijts, Carsten Flohr, Alan D Irvine, Gerard H Koppelman, Young-Ae Lee, Nick J Reynolds, Catherine Smith, Sinéad M Langan, Lavinia Paternoster, Sara J Brown","doi":"10.1111/all.16605","DOIUrl":"https://doi.org/10.1111/all.16605","url":null,"abstract":"<p><strong>Background: </strong>Multiple environmental and genetic factors play a role in the pathogenesis of atopic eczema (AE). We aimed to investigate gene-environment interactions (G × E) to improve understanding of the pathophysiology.</p><p><strong>Methods: </strong>We analysed data from 16 European studies to test for interaction between the 24 most significant AE-associated loci identified from genome-wide association studies and 18 early-life environmental factors. We tested for replication using a further 10 studies and in vitro modeling to independently assess findings.</p><p><strong>Results: </strong>The discovery analysis (including 25,339 individuals) showed suggestive evidence for interaction (p < 0.05) between seven environmental factors (antibiotic use, cat ownership, dog ownership, breastfeeding, elder sibling, smoking and washing practices) and at least one established variant for AE, 14 interactions in total. In the replication analysis (254,532 individuals) dog exposure × rs10214237 (on chromosome 5p13.2 near IL7R) was nominally significant (OR_interaction = 0.91 [0.83-0.99] p = 0.025), with a risk effect of the T allele observed only in those not exposed to dogs. A similar interaction with rs10214237 was observed for siblings in the discovery analysis (OR_interaction = 0.84 [0.75-0.94] p = 0.003), but replication analysis was under-powered (OR_interaction = 1.09 [0.82-1.46]). rs10214237 homozygous risk genotype is associated with lower IL-7R expression in human keratinocytes, and dog exposure modelled in vitro showed a differential response according to rs10214237 genotype.</p><p><strong>Conclusion: </strong>Interaction analysis and functional assessment provide preliminary evidence that early-life dog exposure may modify the genetic effect of rs10214237 on AE via IL7R, supporting observational epidemiology showing a protective effect for dog ownership. The lack of evidence for other G × E studied here implies only weak effects are likely to occur.</p>","PeriodicalId":122,"journal":{"name":"Allergy","volume":" ","pages":""},"PeriodicalIF":12.6,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vulnerability to Pollen-Related Asthma Hospital Admissions in the UK Biobank: A Case-Crossover Study","authors":"Elaine Fuertes,&nbsp;Garyfallos Konstantinoudis,&nbsp;Diana van der Plaat,&nbsp;Adam Koczoski,&nbsp;Mikhail Sofiev,&nbsp;Paul Agnew,&nbsp;Lucy Neal,&nbsp;Debbie Jarvis","doi":"10.1111/all.16612","DOIUrl":"10.1111/all.16612","url":null,"abstract":"&lt;p&gt;In 2023, a systematic review and meta-analysis concluded that outdoor pollen may affect asthma exacerbations in adults [&lt;span&gt;1&lt;/span&gt;]. However, the authors cautioned that the literature is heterogenous and most studies are ecological and have not considered individual-level confounders or effect modifiers.&lt;/p&gt;&lt;p&gt;We here examined associations between daily concentrations of grass pollen, three tree pollens, and nettle pollen (represents weeds) assigned to home addresses using a deterministic model developed by the UK Met Office [&lt;span&gt;2&lt;/span&gt;], and asthma hospital admissions among UK Biobank adult participants [&lt;span&gt;3&lt;/span&gt;] from 2011 to 2022. Effect modification by demographic and environmental factors was examined.&lt;/p&gt;&lt;p&gt;Bidirectional adjusted time-stratified case-crossover models assessed associations between emergency asthma hospital admissions (493 ICD9 or J45/J46 ICD10 codes) and same-day pollen levels (high vs. low) [&lt;span&gt;2&lt;/span&gt;] assigned to home addresses. Further information on data sources and the statistical analysis is in the Supporting Information.&lt;/p&gt;&lt;p&gt;Effect modification by daily mean NO&lt;sub&gt;2&lt;/sub&gt;, PM&lt;sub&gt;2.5&lt;/sub&gt;, and ozone was examined (using tertiles), and models were stratified by annual average NO&lt;sub&gt;2&lt;/sub&gt; and PM&lt;sub&gt;2.5&lt;/sub&gt; levels, % greenspace, sex, age, ethnicity, BMI, smoking, education, income, deprivation (as defined in Table S1), and genetic risk for atopy, the latter as a marker for sensitization (Supporting Information).&lt;/p&gt;&lt;p&gt;There were 1893 asthma emergency hospital admissions (primary diagnosis, &gt; 14 days apart) among 1489 participants from January to September 2011–2022. Descriptive statistics for the pollen variables, study population, and confounders (i.e., meteorological and pollution variables) are provided in Table 1; Tables S1 and S2, respectively.&lt;/p&gt;&lt;p&gt;Asthma hospital admissions were higher on days of high alder and grass concentrations and when considering all pollen types together (Table 1). These findings remained fairly consistent when adjusting for air pollutants (Table S3), examining different lags (Table S4) and restricting to groups and time periods of interest (Table S5). Effect estimates for alder (but not birch) were also elevated when using a second pollen dataset for external validation (European pollen reanalysis, not available for the other pollen types, Table 1) [&lt;span&gt;4&lt;/span&gt;]. The adverse association observed with high grass concentrations is in line with most existing literature, whereas that with alder has been reported in some but not all studies [&lt;span&gt;1&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Associations for several pollens were notably stronger on days with high daily NO&lt;sub&gt;2&lt;/sub&gt; and PM&lt;sub&gt;2.5&lt;/sub&gt; levels (Figure 1), suggesting an acute interactive effect. This observation adds significantly to the currently weak evidence from epidemiological studies of pollution-pollen interactions, despite robust results from in vitro and experimental work [&lt;span&gt;5&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;For some poll","PeriodicalId":122,"journal":{"name":"Allergy","volume":"80 7","pages":"2081-2083"},"PeriodicalIF":12.6,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.16612","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dupilumab Treatment Is Associated With Clinical Improvement and a Shift Toward a Health-Associated Nasal Passage Microbiota in Diffuse Type 2 Chronic Rhinosinusitis","authors":"Fabio S. Ryser,&nbsp;Tomas Demeter,&nbsp;Judith Bergada Pijuan,&nbsp;Srikanth Mairpady Shambat,&nbsp;Catrin Brühlmann,&nbsp;Tina Mauthe,&nbsp;Markus Hilty,&nbsp;Michael B. Soyka,&nbsp;Urs C. Steiner,&nbsp;Silvio D. Brugger","doi":"10.1111/all.16600","DOIUrl":"10.1111/all.16600","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Nasal microbiota composition of patients with diffuse type 2 chronic rhinosinusitis with nasal polyps (CRSwNP) is altered compared to healthy individuals. Dupilumab, an anti-IL-4Rα-mAb, modulates type 2 inflammation, but the effect on microbiota composition in CRSwNP is unknown. The aim of this study was to investigate longitudinal effects of dupilumab on the nasal passage and gastrointestinal microbiota in patients with diffuse type 2 CRSwNP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Twenty-seven patients with diffuse type 2 CRSwNP treated with dupilumab 300 mg subcutaneously every 2 weeks, 10 untreated patients with CRSwNP, and 11 healthy controls were included. Nasal and stool samples were collected at Days 0, 28, 90, and 180 posttreatment of the treated CRSwNP group and at Days 0 and 28 of untreated CRSwNP and healthy controls. The samples were analyzed using 16S rRNA gene amplicon sequencing (V3/V4).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In CRSwNP patients, the most abundant genera in nasal passage microbiota were <i>Corynebacterium</i> and <i>Staphylococcus</i>. <i>Cutibacterium</i> and <i>Lawsonella</i> were less abundant in CRSwNP at baseline compared to healthy controls. Dupilumab treatment was associated with increased relative abundances in the nasal passage of genera such as <i>Lawsonella, Corynebacterium</i>, and <i>Dolosigranulum</i>. Microbial diversity of the gastrointestinal microbiota in CRSwNP at baseline was significantly higher than in healthy controls. There were no changes in gastrointestinal microbiota during dupilumab treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Dupilumab treatment was associated with a shift in the nasal passage bacterial microbiota toward that of healthy controls, whereas the composition of gastrointestinal microbiota did not change. These findings suggest that nasal passage microbiota composition is influenced by the underlying inflammatory endotype.</p>\u0000 </section>\u0000 </div>","PeriodicalId":122,"journal":{"name":"Allergy","volume":"80 6","pages":"1746-1756"},"PeriodicalIF":12.6,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.16600","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144193115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Subcutaneous Allergen Immunotherapy With Hypoallergenic Bet v 1 Compared to Conventional Extract: Poorer Blocking Antibody Capacity Dominated by IgG1 Instead of IgG4","authors":"Lorenz Aglas,&nbsp;Line Kring Tannert,&nbsp;Serge A. Versteeg,&nbsp;Scott A. Smith,&nbsp;Ewa A. Bartko,&nbsp;Mario Wenger,&nbsp;Amin Kraiem,&nbsp;Hannah Widauer,&nbsp;Natália Nunes,&nbsp;Sibile Sinkunaite,&nbsp;Frank Stolz,&nbsp;Laurian Jongejan,&nbsp;Angela Neubauer,&nbsp;Lars H. Blom,&nbsp;Fatima Ferreira,&nbsp;Lars K. Poulsen,&nbsp;Carsten Bindslev-Jensen,&nbsp;Ronald van Ree","doi":"10.1111/all.16606","DOIUrl":"10.1111/all.16606","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hypoallergenic recombinant fold-variants of major allergens have been suggested as safer and more effective AIT candidates. The Bet v 1-fold variant BM41, with confirmed preclinical hypoallergenicity and increased immunogenicity, was proposed for the treatment of birch pollen allergy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed a 6-month randomized, double-blind, placebo-controlled first-in-human clinical trial with BM41, a licensed birch pollen extract-based treatment, as the active comparator (AC), and placebo (<i>n</i> = 16, <i>n</i> = 16, and <i>n</i> = 15, respectively). The primary endpoint was safety. Secondary outcomes were Bet v 1-specific (s)IgE, IgG, IgG₁, and IgG₄ responses measured by ImmunoCAP, and sIgE-blocking activity using mediator release and facilitated antigen binding assays.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Despite SPT-confirmed hypoallergenicity (~50% compared to natural Bet v 1), more adverse events occurred in response to BM41. Although similar sIgG and sIgG₁ levels were induced, sIgG₄ levels increased 3-fold more in AC compared to the BM41 group. In AC, the sIgG₄/sIgG₁ ratio tripled over time, whereas for BM41 it stagnated. BM41 induced efficient serum inhibitory activity for sIgE compared to placebo but was 12%–32% less efficient than AC. Both sIgG₄ and sIgG₁ contributed to the blocking effect in AC, while in BM41 both sIgG subclasses showed a lowered functional capacity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Preclinically established hypoallergenicity of BM41 did not result in a lower number of adverse events. The reduced induction of sIgG₄ by the fold variant in the course of the treatment was less efficient in blocking sIgE-mediated responses. This is the first study providing evidence that, instead of a Th1-favored IgG₁-dominated response, “modified Th2”-skewed IgG₄-dominated humoral responses are beneficial in AIT vaccine design.</p>\u0000 </section>\u0000 </div>","PeriodicalId":122,"journal":{"name":"Allergy","volume":"80 7","pages":"2018-2030"},"PeriodicalIF":12.6,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.16606","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aerosol Measurements and Decadal Changes: The Role of Climatic Changes and How It Reflects in Respiratory Allergies and Asthma","authors":"Stelios Kazadzis,&nbsp;Illias Fountoulakis,&nbsp;Athanasios Damialis,&nbsp;Akriti Masoom,&nbsp;Kyriakoula Papachristopoulou,&nbsp;Stefanie Gilles,&nbsp;Martine Collaud Coen,&nbsp;Fiona Tummon,&nbsp;Benoît Crouzy,&nbsp;Bernard Clot,&nbsp;Yagiz Pat,&nbsp;Marie-Charlotte Brüggen,&nbsp;Stephan Nyeki,&nbsp;Ioannis-Panagiotis Raptis,&nbsp;Stavros Solomos,&nbsp;Antonis Gkikas,&nbsp;Anna Moustaka,&nbsp;Natalia Kouremeti,&nbsp;Cezmi A. Akdis","doi":"10.1111/all.16602","DOIUrl":"10.1111/all.16602","url":null,"abstract":"<p>The causative agents of respiratory allergies are bioaerosols, such as house dust mite feces, pollen grains, and fungal spores. Climate change and urbanization are considered to lead to an increase in the load of allergenic bioaerosols due to impacts on plant phenophases and allergenicity. Continuous and efficient monitoring of the atmospheric composition worldwide is essential, given the major changes involved and their impact on climate change. The complexity of the exposome, evolving from single to multiple complex exposures, is explored in this work. Acquiring information from interdisciplinary scientific disciplines, such as aerobiology (for airborne particles of biological origin), aerosol science (for airborne particles of chemical or inorganic material), and integrating this with the actual reactome of patients with respiratory diseases, we aim to provide evidence of the multifactorial nature of this interaction in real life. The objective of this review is to present how we can monitor aerosols and mostly monitor the exposome, especially the biological one, i.e., pollen and fungal spores, and what their impact is, or could be, on respiratory allergies. A huge technological advancement has been required, as traditional methods of particle collection and identification have been based on tedious laboratory procedures, with delays of more than a week. This has limited their practical use to allergic patients and their treating physicians. Automation, real-time high temporal resolution, and the use of artificial intelligence are being increasingly used in medicine. Likewise, this overview summarizes the current aerosol measurement and modeling capabilities and discusses the classification of various aerosol particles and their impact on respiratory allergies. Satellite remote sensing is highlighted as a solution to the gaps in global aerosol representation by examining aerosol load in the atmospheric column in major cities worldwide. We also discuss potential novel threats, such as pioneer bioaerosols and the respiratory epithelial barrier, as well as future insights into the impact of climate change on allergy and asthma. We conclude with a discussion of emerging co-exposures and co-diseases resulting from the ongoing climate change.</p>","PeriodicalId":122,"journal":{"name":"Allergy","volume":"80 6","pages":"1613-1628"},"PeriodicalIF":12.6,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.16602","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144188967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correspondence: Cellular Rhinitis-A Key Yet Overlooked Factor in the Management of Otitis Media With Effusion (OME) and Eustachian Tube Dysfunction (ETD).","authors":"Matteo Gelardi","doi":"10.1111/all.16609","DOIUrl":"https://doi.org/10.1111/all.16609","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":"35 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144146137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}