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Reduced Type-I Interferon by Plasmacytoid Dendritic Cells and Asthma in School-Aged Children. 浆细胞样树突状细胞降低i型干扰素与学龄期儿童哮喘的关系。
IF 12.4 1区 医学
Allergy Pub Date : 2025-08-13 DOI: 10.1111/all.70005
Isabelle Coenen,Anya C Jones,Alice A White,Mari Takashima,Wen Ray Lee,Matthew D Wong,Dwan Vilcins,Ulrich Kadolsky,Ali Sadiq Cheema,Alka Saxena,Anthony Bosco,Keith Grimwood,Peter D Sly,Deborah H Strickland,Jonatan Leffler
{"title":"Reduced Type-I Interferon by Plasmacytoid Dendritic Cells and Asthma in School-Aged Children.","authors":"Isabelle Coenen,Anya C Jones,Alice A White,Mari Takashima,Wen Ray Lee,Matthew D Wong,Dwan Vilcins,Ulrich Kadolsky,Ali Sadiq Cheema,Alka Saxena,Anthony Bosco,Keith Grimwood,Peter D Sly,Deborah H Strickland,Jonatan Leffler","doi":"10.1111/all.70005","DOIUrl":"https://doi.org/10.1111/all.70005","url":null,"abstract":"BACKGROUNDAllergic sensitization and reduced ability to respond to viral infections may contribute to virus-induced wheeze and asthma development in young children. Plasmacytoid dendritic cells (pDC) are rare immune cells that produce type I interferons (IFN-I) and play a key role in orchestrating immune responses against viruses.OBJECTIVETo further evaluate the function of pDC in children with asthma.METHODSThis study was based on a subset of 71 children from the Early Life Lung Function (ELLF) cohort at the age of 7 years. As part of the ELLF study, participants were characterized for atopic sensitization, viral infection history, and lung function testing. pDC responses to a TLR7/8 agonist were assessed in the presence or absence of anti-IgE using an in vitro assay. Responses were evaluated utilizing flow cytometry, multiplexed cytokine assays, and transcriptional analysis of isolated pDC.RESULTSpDC responses varied considerably across individuals, and those who responded with IFN-I following stimulation showed a lower proportion of asthma compared to those who responded with TNF-only. A TNF-only response was associated with increased atopy and reduced upregulation of IFN-associated genes. Anti-IgE stimulation reduced pDC activation, and the reduction was associated with baseline expression of the IgE receptor (FcεR1). A reduction in a gene module centralized around genes such as TPM2, LILRA4, and CLEC4C was also observed.CONCLUSIONTogether, these findings suggest that pDC responses are variable, associated with asthma, and appear influenced by environmental stimuli. This response thus appears to be an important aspect of asthma pathology in children.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"1 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144825664","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}
引用次数: 0
Occupational Mite Allergy and Asthma: An EAACI Task Force Report 职业性螨虫过敏和哮喘:EAACI工作组报告。
IF 12 1区 医学
Allergy Pub Date : 2025-08-13 DOI: 10.1111/all.16666
Hille Suojalehto, Mohamed F. Jeebhay, Ingrid Sander, Santiago Quirce, Susanne Vrtala, Jolanta Walusiak-Skorupa, Andreas L. Lopata, Carmen Vidal, Monika Raulf
{"title":"Occupational Mite Allergy and Asthma: An EAACI Task Force Report","authors":"Hille Suojalehto,&nbsp;Mohamed F. Jeebhay,&nbsp;Ingrid Sander,&nbsp;Santiago Quirce,&nbsp;Susanne Vrtala,&nbsp;Jolanta Walusiak-Skorupa,&nbsp;Andreas L. Lopata,&nbsp;Carmen Vidal,&nbsp;Monika Raulf","doi":"10.1111/all.16666","DOIUrl":"10.1111/all.16666","url":null,"abstract":"<p>Mite sensitization is notable in several occupational settings. Elevated house dust mite concentrations are primarily detected in workplaces where people congregate and are active. Allergy to storage mites and spider mites has commonly been reported in agricultural and various food processing occupations. Rapid expansion of biological pest control has resulted in increased exposure to predatory mites causing sensitization of greenhouse workers. Globally, mite populations in workplaces are likely to change due to climate change. Occupational relevant mites produce a variety of allergens and adjuvants that trigger both innate and adaptive immune responses. Cross-reactivity between allergens occurs due to shared IgE-binding epitopes to different allergens. Occupational allergy to mites typically causes rhinitis and asthma. Challenges of distinguishing the role of occupational exposure to allergens, also present in non-occupational environments, complicate the diagnosis of occupational mite allergy and asthma. Nevertheless, preventive measures to reduce exposure to mite allergens in workplaces are essential in mitigating occupational hazards. Further research is needed to better understand the incidence of occupational mite allergy and asthma. It is essential to identify the risk factors in different occupational settings, assess the impact of climate change on exposure, and determine the relevant allergens and their potential cross-reactivity.</p>","PeriodicalId":122,"journal":{"name":"Allergy","volume":"80 9","pages":"2484-2500"},"PeriodicalIF":12.0,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.16666","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144825662","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}
引用次数: 0
The Basophil Activation Test Is the Most Accurate Test in Predicting Allergic Reactions to Baked and Fresh Cow's Milk During Oral Food Challenges 嗜碱性粒细胞激活试验是预测在口服食物挑战中对烤牛奶和新鲜牛奶过敏反应最准确的试验。
IF 12 1区 医学
Allergy Pub Date : 2025-08-13 DOI: 10.1111/all.16675
Irene Bartha, Holly Boyd, Ru-Xin Foong, Marta Krawiec, Andreina Marques-Mejias, Hannah F. Marshall, Suzana Radulovic, Faye Harrison, Grammatiki Antoneria, Zainab Jama, Matthew Kwok, Ewa Pietraszewicz, Malak Eghleilib, Cristian Ricci, Tom Marrs, Gideon Lack, George Du Toit, Alexandra F. Santos
{"title":"The Basophil Activation Test Is the Most Accurate Test in Predicting Allergic Reactions to Baked and Fresh Cow's Milk During Oral Food Challenges","authors":"Irene Bartha,&nbsp;Holly Boyd,&nbsp;Ru-Xin Foong,&nbsp;Marta Krawiec,&nbsp;Andreina Marques-Mejias,&nbsp;Hannah F. Marshall,&nbsp;Suzana Radulovic,&nbsp;Faye Harrison,&nbsp;Grammatiki Antoneria,&nbsp;Zainab Jama,&nbsp;Matthew Kwok,&nbsp;Ewa Pietraszewicz,&nbsp;Malak Eghleilib,&nbsp;Cristian Ricci,&nbsp;Tom Marrs,&nbsp;Gideon Lack,&nbsp;George Du Toit,&nbsp;Alexandra F. Santos","doi":"10.1111/all.16675","DOIUrl":"10.1111/all.16675","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cow's milk is the most common cause of food allergy and related fatalities. Consumption of baked milk (BM) has been associated with better prognosis, nutrition and quality-of-life.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The BAT 2 milk study (NCT03309488) was a diagnostic study of cow's milk allergy designed according to STARD guidelines. All children had an oral food challenge (OFC) to BM, and those who tolerated BM were offered an OFC to fresh milk (FM). The diagnostic performance of the basophil activation test (BAT), skin prick test (SPT) and specific IgE (sIgE) was assessed in comparison with OFC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Out of the 150 children studied, 85% tolerated BM and 56% also tolerated FM. BAT had the best diagnostic accuracy (area under the receiver operator characteristic curve 0.90 for BM and 0.81 for FM) compared with the other tests for both BM (sIgE: 0.79 and SPT: 0.70) and FM (sIgE: 0.74 and SPT: 0.78) allergies. Using 100% sensitivity and 100% specificity cut-offs to select patients for OFC would have led to the following proportion of children having OFC (and positive OFC) to BM: 99% (13%) for SPT to baked milk, 82% (17%) for sIgE to boiled milk, and 49% (24%) for BAT to baked milk. In children younger than 2 years, only 27% required an OFC following BAT to BM (compared to 100% and 81% following SPT or sIgE to milk extract, respectively), with 100% diagnostic accuracy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>BAT was the best test to identify children who reacted on OFC to BM or FM. Using 100% sensitivity and 100% specificity cut-offs, BAT ensured the lowest need for OFC and 100% diagnostic accuracy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>clinicaltrials.gov identifier: NCT03309488</p>\u0000 </section>\u0000 </div>","PeriodicalId":122,"journal":{"name":"Allergy","volume":"80 10","pages":"2861-2873"},"PeriodicalIF":12.0,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.16675","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144843877","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}
引用次数: 0
Cell Type-Specific IL-5Rα Distribution and IL-5-Induced CCL11 Expression in Human Nasal Epithelium 人鼻上皮细胞类型特异性IL-5Rα分布及il -5诱导的CCL11表达
IF 12 1区 医学
Allergy Pub Date : 2025-08-11 DOI: 10.1111/all.70003
Yosep Kim, Miran Kang, Juhee Seo, Subin Kim, Min-Seok Rha, Chang-Hoon Kim, Hyung-Ju Cho
{"title":"Cell Type-Specific IL-5Rα Distribution and IL-5-Induced CCL11 Expression in Human Nasal Epithelium","authors":"Yosep Kim,&nbsp;Miran Kang,&nbsp;Juhee Seo,&nbsp;Subin Kim,&nbsp;Min-Seok Rha,&nbsp;Chang-Hoon Kim,&nbsp;Hyung-Ju Cho","doi":"10.1111/all.70003","DOIUrl":"10.1111/all.70003","url":null,"abstract":"&lt;p&gt;Allergic airway diseases alter epithelial composition through Th2 cytokines, particularly IL-4, IL-13, and IL-5 [&lt;span&gt;1&lt;/span&gt;]. While IL-5 signaling is traditionally associated with eosinophil regulation via its receptor (IL-5R) [&lt;span&gt;2&lt;/span&gt;], its role in epithelial cell function remains incompletely understood. IL-5 synergizes with eotaxins in the airways to recruit eosinophils, emphasizing its role in inflammatory cell recruitment [&lt;span&gt;3&lt;/span&gt;]. Recent studies have demonstrated IL-5R expression in bronchial epithelial cells [&lt;span&gt;4&lt;/span&gt;], but there are conflicting reports about its functionality in nasal epithelial cells [&lt;span&gt;5&lt;/span&gt;]. Our study reveals previously unrecognized expression patterns of IL-5R in airway epithelium that may significantly influence therapeutic responses to biologics, particularly in allergic airway diseases.&lt;/p&gt;&lt;p&gt;Using single-cell RNA sequencing of human nasal epithelial cells from healthy controls, we discovered that IL-5Rα expression is predominantly restricted to deuterosomal and multiciliated cells, contrasting with the broader expression of IL-4R and IL-13Rα1 across cell types. Immunofluorescence staining revealed that IL-4R colocalizes with MUC5AC-positive goblet cells in nasal epithelium (Figure S4). IL-13Rα2 showed minimal expression in all populations. This distinct pattern was consistently observed in both ex vivo nasal epithelial cells and in vitro cultures, with IL-4 exposure notably decreasing IL-5Rα expression while modulating other key differentiation markers (Figure 1A–C).&lt;/p&gt;&lt;p&gt;Immunofluorescence analysis confirmed these findings, demonstrating clear IL-5Rα colocalization with acetylated-tubulin (a multiciliated cell marker) in healthy tissues while showing markedly reduced expression in eosinophilic or non-eosinophilic nasal polyp tissues (Figure 1D). Importantly, IL-5Rα showed no colocalization with MUC5AC (a goblet cell marker) under any conditions (Figure 1E,F), establishing its specific localization to the apical surface of multiciliated cells.&lt;/p&gt;&lt;p&gt;Further molecular analysis revealed that IL-4 exposure reduced both IL-5Rα mRNA and protein levels while upregulating MUC5AC expression and modulating other epithelial markers, including KRT5, SOX2, CD44v3, and MUC5B (Figure 2A–G, Figure S5). Consistent with previous studies on airway remodeling in type 2 inflammation [&lt;span&gt;1, 6&lt;/span&gt;], our in vitro stimulation with IL-4 resulted in a significant reduction of multiciliated cells with concurrent goblet cell hyperplasia. IL-5R mRNA expression was significantly higher in differentiated (ALI) than in undifferentiated human nasal epithelial cells, with IL-4 suppressing and IL-5 maintaining this expression pattern in differentiated cells only (Figure S1). We further demonstrate that altered expression patterns of key cytokine receptors accompany this phenotypic shift. Since IL-5Rα is present in epithelial cells, we hypothesized that IL-5 could directly stimulate epithelial cells. To tes","PeriodicalId":122,"journal":{"name":"Allergy","volume":"80 9","pages":"2654-2659"},"PeriodicalIF":12.0,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.70003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144813127","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}
引用次数: 0
IgG4-Related Disease: Emerging Roles of Novel Genetic Variants, Immune Cell Subsets and Therapeutic Targets igg4相关疾病:新基因变异、免疫细胞亚群和治疗靶点的新角色
IF 12 1区 医学
Allergy Pub Date : 2025-08-11 DOI: 10.1111/all.16686
Louisa Tedesco, Syed B. Ali, Baran Erman, Safa Baris, Harshita Pant, Pravin Hissaria, Yelda Bilginer, Damon J. Tumes, Gökhan Cildir
{"title":"IgG4-Related Disease: Emerging Roles of Novel Genetic Variants, Immune Cell Subsets and Therapeutic Targets","authors":"Louisa Tedesco,&nbsp;Syed B. Ali,&nbsp;Baran Erman,&nbsp;Safa Baris,&nbsp;Harshita Pant,&nbsp;Pravin Hissaria,&nbsp;Yelda Bilginer,&nbsp;Damon J. Tumes,&nbsp;Gökhan Cildir","doi":"10.1111/all.16686","DOIUrl":"10.1111/all.16686","url":null,"abstract":"<p>IgG4, the least abundant IgG subclass in humans, is increasingly recognised for its involvement in allergic and autoimmune pathologies. Its unique properties, such as the tendency to form half-molecules (one heavy chain and one light chain) and its generally non-inflammatory nature, distinguish it from other IgG subclasses. Its role in immune dysregulation is further underscored by a distinct disease entity called IgG4-related disease (IgG4-RD), a systemic fibroinflammatory disorder characterised by IgG4<sup>+</sup> plasma cell tissue infiltration, storiform fibrosis and obliterative phlebitis, reflecting a dysregulated immune response affecting multiple organs. This review examines the current understanding of IgG4, its emerging roles in immune dysregulation and IgG4-RD, including clinical manifestations and treatment options. We also discuss the recent advances in understanding the genetic underpinnings of IgG4-RD, highlighting the significance of germline gene variants and implicated immune cell types. Finally, we explore future research directions, emphasising the need for deeper insights into pathogenesis, specific biomarkers and optimised treatment strategies.</p>","PeriodicalId":122,"journal":{"name":"Allergy","volume":"80 10","pages":"2738-2754"},"PeriodicalIF":12.0,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.16686","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144813125","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}
引用次数: 0
Decrease in Eosinophil-Derived-Neurotoxin With Mepolizumab Is Associated With Asthma Improvement Mepolizumab治疗中嗜酸性粒细胞衍生神经毒素的减少与哮喘改善相关
IF 12 1区 医学
Allergy Pub Date : 2025-08-11 DOI: 10.1111/all.70008
Vanessa Granger, Rachel Nadif, Laurent Orsi, Sylvie Chollet Martin, Luc de Chaisemartin, Camille Taillé
{"title":"Decrease in Eosinophil-Derived-Neurotoxin With Mepolizumab Is Associated With Asthma Improvement","authors":"Vanessa Granger,&nbsp;Rachel Nadif,&nbsp;Laurent Orsi,&nbsp;Sylvie Chollet Martin,&nbsp;Luc de Chaisemartin,&nbsp;Camille Taillé","doi":"10.1111/all.70008","DOIUrl":"10.1111/all.70008","url":null,"abstract":"&lt;p&gt;Over the past decade, mepolizumab, an anti-IL-5 monoclonal antibody, has been introduced to target eosinophils in severe asthma. Despite its well-documented efficacy [&lt;span&gt;1, 2&lt;/span&gt;], recent studies have highlighted a heterogeneous clinical response among patients [&lt;span&gt;3&lt;/span&gt;], underscoring the need to identify biomarkers to monitor response to mepolizumab. Currently, eosinophilic inflammation is monitored through eosinophil cell counts, which provide only a limited evaluation of eosinophil activity. Indeed, asthma is characterized not only by an increased number of eosinophils but also by enhanced airway eosinophil degranulation. Although a high blood eosinophil count is associated with treatment response, its extreme variability limits its utility as a biomarker. Similarly, sputum eosinophil counts, while informative, are not routinely available in clinical practice. Given these limitations, recent studies have focused on eosinophil-derived neurotoxin (EDN), a promising stable biomarker of eosinophil degranulation, for asthma monitoring [&lt;span&gt;4-6&lt;/span&gt;]. However, the evolution of EDN levels in response to anti-IL-5 therapies remains poorly documented. In this study, we compared EDN levels and eosinophil counts in both blood and bronchoalveolar lavage fluid (BALF) as markers of response to mepolizumab in patients with severe asthma (NCT03797404). EDN was measured at baseline (D0), at 6 months (M6), and at 12 months (M12) using a fluorescence enzyme immunoassay. Regression models were employed to assess associations between the absolute variation in EDN levels (M6-D0) in blood and BALF and concurrent changes in asthma-related characteristics, including disease control, pulmonary function, and exacerbation frequency. Twenty patients with complete D0-M6 EDN kinetics in both BALF and blood were included in the longitudinal analyses (Figure S1). Detailed methods are presented in Appendix S1 and baseline clinical characteristics in Table S1. Additionally, results from a subgroup of 14 patients who underwent an additional bronchoscopy at 12 months are presented in Table S2.&lt;/p&gt;&lt;p&gt;Baseline EDN levels did not differ significantly between BALF and serum both in the 6 months longitudinal population (median = 46 ng/mL vs 146/mL; &lt;i&gt;p&lt;/i&gt; = 0.9) and in the 12 months longitudinal population (median = 37 ng/mL vs 118 ng/mL; &lt;i&gt;p&lt;/i&gt; = 0.8). At baseline, blood and BALF EDN levels were correlated, as were blood and alveolar eosinophil counts (&lt;i&gt;r&lt;/i&gt; = 0.522, &lt;i&gt;p&lt;/i&gt; = 0.02 and &lt;i&gt;r&lt;/i&gt; = 0.716, &lt;i&gt;p&lt;/i&gt; = 0.0006, respectively) (Figure 1A,B). Additionally, EDN levels and eosinophil counts were correlated within both compartments (&lt;i&gt;r&lt;/i&gt; = 0.643, &lt;i&gt;p&lt;/i&gt; = 0.002 and &lt;i&gt;r&lt;/i&gt; = 0.715, &lt;i&gt;p&lt;/i&gt; = 0.0006, respectively) (Figure 1C,D).&lt;/p&gt;&lt;p&gt;As expected, mepolizumab led to a significant improvement in asthma control and a reduction in the exacerbation rate (Tables S2 and S3).&lt;/p&gt;&lt;p&gt;EDN level dramatically decreased 6 months after mepolizumab initiation","PeriodicalId":122,"journal":{"name":"Allergy","volume":"80 9","pages":"2663-2666"},"PeriodicalIF":12.0,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.70008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812946","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}
引用次数: 0
An Inflammation-Associated Control Mechanism of Allergy by Proteolysis of IgE IgE蛋白水解对过敏的炎症相关控制机制。
IF 12 1区 医学
Allergy Pub Date : 2025-08-10 DOI: 10.1111/all.16622
Estefania Ugarte-Berzal, Erik Martens, Rafaela Vaz Sousa Pereira, Dries Wets, Eva Ganseman, Mieke Gouwy, Christine Breynaert, Christine Guntermann, Rik Schrijvers, Paul Proost, Ghislain Opdenakker
{"title":"An Inflammation-Associated Control Mechanism of Allergy by Proteolysis of IgE","authors":"Estefania Ugarte-Berzal,&nbsp;Erik Martens,&nbsp;Rafaela Vaz Sousa Pereira,&nbsp;Dries Wets,&nbsp;Eva Ganseman,&nbsp;Mieke Gouwy,&nbsp;Christine Breynaert,&nbsp;Christine Guntermann,&nbsp;Rik Schrijvers,&nbsp;Paul Proost,&nbsp;Ghislain Opdenakker","doi":"10.1111/all.16622","DOIUrl":"10.1111/all.16622","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Adaptive IgE-mediated reactions are faster than immune responses that depend on IgM, IgA, and IgG. Normal serum IgE concentrations are highly variable among individuals and extremely low in comparison with those of IgM and IgG. Omalizumab is a clinically approved monoclonal antibody that selectively binds free IgE, preventing allergy-specific IgE from binding to FcεRI expressed on mast cells and basophils, thereby inhibiting degranulation and mediator release. We aimed to evaluate proteolysis of IgE within the contexts of acute inflammations in vitro and in patient samples and the biological effects of resulting IgE proteoforms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>IgE was subjected in vitro to neutrophil proteases. Biochemical and biological IgE proteoform identification was performed and IgE receptor binding capacity and abundance in patient samples were evaluated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Whereas IgG, IgA, and IgM are neutrophil protease-resistant, the IgE heavy chain was cleaved in a bait region by these inflammation-associated proteases. The cleavages occurred on both free and CD23-bound IgE; however, not with FcεRI-bound IgE. Proteolysis generated two proteoforms: a large IgE cleavage fragment (IgEcl) and a smaller IgE carboxyterminal truncation fragment Cεtr. Proteolysed IgE did not bind to its receptors. The Cεtr fragment shared with chemokines high affinity to glycosaminoglycans (GAGs) and synergistically attracted neutrophils. The discovered bait region in IgE corresponded with a shared epitope recognized by omalizumab, and omalizumab prevented IgE proteolysis. Both IgEcl and Cεtr were present in plasma samples from patients suffering from IgE-mediated allergies, chronic spontaneous urticaria, and more abundantly in atopic dermatitis (AD) patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This work reveals new mechanistic insights into the immunobiology of IgE and the action of omalizumab with potential clinical impacts. Indeed, IgE-specific cleavage by inflammation-associated granulocyte proteinases may be an important feedback mechanism to control allergic responses.</p>\u0000 </section>\u0000 </div>","PeriodicalId":122,"journal":{"name":"Allergy","volume":"80 10","pages":"2781-2799"},"PeriodicalIF":12.0,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144813129","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}
引用次数: 0
Epithelial Memory After Respiratory Viral Infection in Mice Results in Prolonged Enhancement of Antigen Presentation 小鼠呼吸道病毒感染后的上皮记忆导致抗原呈递的延长增强。
IF 12 1区 医学
Allergy Pub Date : 2025-08-07 DOI: 10.1111/all.16683
Piotr P. Janas, Wouter T'Jonck, Matthew O. Burgess, Maximilian Reck, Caroline Chauché, Matthieu Vermeren, Christopher D. Lucas, Calum Bain, Robert Illingworth, Edward W. Roberts, Henry J. McSorley, Jürgen Schwarze
{"title":"Epithelial Memory After Respiratory Viral Infection in Mice Results in Prolonged Enhancement of Antigen Presentation","authors":"Piotr P. Janas,&nbsp;Wouter T'Jonck,&nbsp;Matthew O. Burgess,&nbsp;Maximilian Reck,&nbsp;Caroline Chauché,&nbsp;Matthieu Vermeren,&nbsp;Christopher D. Lucas,&nbsp;Calum Bain,&nbsp;Robert Illingworth,&nbsp;Edward W. Roberts,&nbsp;Henry J. McSorley,&nbsp;Jürgen Schwarze","doi":"10.1111/all.16683","DOIUrl":"10.1111/all.16683","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Viral lower respiratory tract infections (LRTIs) can reduce the severity of subsequent LRTIs but have also been linked to respiratory allergy development and exacerbation. Here, we show that viral LRTI can imprint lung epithelial cells (LECs), leading to prolonged phenotypic and functional changes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Mice were infected via intranasal administration of respiratory syncytial virus (RSV). After 28 days, LECs were isolated using cold dispase digestion followed by magnetic-activated cell sorting. Epigenetic changes were assessed using Cleavage Under Targets and Release Using Nuclease (CUT&amp;RUN), while transcriptional changes were evaluated using NanoString and qPCR. Flow cytometry was employed to measure cell surface major histocompatibility complex (MHC) levels, antigen uptake and processing rates, and OT-I cell proliferation after antigen presentation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified epigenetic and transcriptomic changes in murine LECs 28 days after RSV infection, especially impacting genes associated with MHC. Lasting upregulation of MHC-I and MHC-II was further increased following in vivo LPS stimulation. Importantly, MHC upregulation was associated with increased antigen uptake and processing, as well as increased antigen presentation to T cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our data demonstrate that RSV can induce prolonged upregulation of antigen presentation by LECs, with the potential to facilitate local T cell responses to microbial antigens and allergens and to enhance immunity or in susceptible hosts respiratory allergy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":122,"journal":{"name":"Allergy","volume":"80 9","pages":"2501-2518"},"PeriodicalIF":12.0,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.16683","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144792036","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}
引用次数: 0
Altered Phage-Related Gene Profiles in Asthmatic Airways. 哮喘气道中噬菌体相关基因谱的改变
IF 12.4 1区 医学
Allergy Pub Date : 2025-08-07 DOI: 10.1111/all.70009
Min-Gyung Baek,Sangcheol Park,Young-Chan Kim,Kyoung-Hee Sohn,Jung Wook Kim,Kwang Jun Lee,Sang-Heon Cho,Hye-Ryun Kang,Hana Yi
{"title":"Altered Phage-Related Gene Profiles in Asthmatic Airways.","authors":"Min-Gyung Baek,Sangcheol Park,Young-Chan Kim,Kyoung-Hee Sohn,Jung Wook Kim,Kwang Jun Lee,Sang-Heon Cho,Hye-Ryun Kang,Hana Yi","doi":"10.1111/all.70009","DOIUrl":"https://doi.org/10.1111/all.70009","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":"31 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144792035","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}
引用次数: 0
Correspondence: Dupilumab-Induced Blood Eosinophilia-Why We Need to Look Beyond the Blood. 对应:dupilumab诱导的嗜酸性血友病-为什么我们需要超越血液。
IF 12.4 1区 医学
Allergy Pub Date : 2025-08-04 DOI: 10.1111/all.70002
Matteo Gelardi,Rossana Giancaspro,Michele Cassano
{"title":"Correspondence: Dupilumab-Induced Blood Eosinophilia-Why We Need to Look Beyond the Blood.","authors":"Matteo Gelardi,Rossana Giancaspro,Michele Cassano","doi":"10.1111/all.70002","DOIUrl":"https://doi.org/10.1111/all.70002","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":"45 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144769614","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}
引用次数: 0
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