Journal of Allergy and Clinical Immunology最新文献

{"title":"Barzolvolimab blocks SCF-enhanced IgE activation without inducing apoptosis in KIT-D816V mast cells.","authors":"Mengjie Hu, Jiajun He, Yanyan Luo, Diego Alvarado, Duncan C Miller, Jörg Scheffel, Stefan Frischbutter, Frank Siebenhaar, Polina Pyatilova","doi":"10.1016/j.jaci.2026.08.019","DOIUrl":"https://doi.org/10.1016/j.jaci.2026.08.019","url":null,"abstract":"<p><strong>Background: </strong>KIT D816V drives constitutive mast cell (MC) signaling and is central to the pathogenesis of clonal mast cell activation disorders including systemic mastocytosis. These conditions may present with severe anaphylaxis despite low KIT D816V mutation burden. Since neoplastic mast cells may co-express mutant and wild-type (WT) KIT, the functional relevance of ligand-dependent signaling and activation remains incompletely understood. Barzolvolimab has demonstrated efficacy in WT MC-driven diseases, but its effects on KIT-mutated MCs remain unclear.</p><p><strong>Objective: </strong>To assess the effects of barzolvolimab on KIT D816V-mutated MCs.</p><p><strong>Methods: </strong>We established and characterized primary-like human MC models, including isogenic hiPSC-derived WT and heterozygous KIT D816V MCs, PSC-derived MCs and HMC-1.2 cell line. Barzolvolimab effects on apoptosis, KIT signaling, and IgE-mediated activation were investigated using flow cytometry, Western blotting, and functional degranulation assays.</p><p><strong>Results: </strong>Barzolvolimab induced dose-dependent apoptosis and inhibited SCF-induced KIT signaling in WT MCs, but had no effect on mutant MC viability or signaling. Notably, barzolvolimab effectively suppressed SCF-enhanced IgE-mediated MC activation across all primary-like models, including KIT D816V MCs, as evidenced by reduced β-hexosaminidase release and CD63 expression. This inhibitory effect occurred at low nanomolar concentrations and was independent of cytotoxicity.</p><p><strong>Conclusions: </strong>Our findings demonstrate a functional dissociation between KIT-dependent survival and activation pathways in mutated MCs. While barzolvolimab does not reduce the viability of KIT-mutated MCs, it effectively suppresses SCF-dependent amplification of IgE-mediated activation, supporting its potential as a therapeutic option for symptomatic patients harboring KIT mutations, particularly for the control of mediator-related symptoms.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891695","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":"Dupilumab efficacy and safety in patients with allergic bronchopulmonary aspergillosis.","authors":"Arnaud Bourdin, Jonathan Corren, Anand Shah, Caroline G Baxter, Lavinia Davidescu, Heather Paleczny, Joseph A Chiarappa, Andrew P Fontenot, Paula Dakin, Elizabeth Laws, Jennifer Maloney, Lacey B Robinson, George D Yancopoulos, Allen Radin","doi":"10.1016/j.jaci.2026.08.021","DOIUrl":"https://doi.org/10.1016/j.jaci.2026.08.021","url":null,"abstract":"<p><strong>Background: </strong>Allergic bronchopulmonary aspergillosis (ABPA) is a complex allergic hypersensitivity reaction to Aspergillus species that can complicate and worsen concomitant asthma and is associated with an intense type 2 immune response in lower airways; there are no approved targeted therapies.</p><p><strong>Objective: </strong>To investigate dupilumab, a fully human monoclonal antibody blocking interleukins 4/13 via the shared interleukin 4 receptor alpha, in patients with asthma and ABPA.</p><p><strong>Methods: </strong>In this double-blind phase 2 trial, patients with asthma aged ≥12 years who met the clinical criteria for ABPA were randomized to dupilumab (n=35) or placebo (n=27) for 24 to 52 weeks; 37.1% were receiving chronic systemic corticosteroids (SCS). The primary endpoint was change from baseline in prebronchodilator forced expiratory volume in 1 second (FEV₁) at 24 weeks. Additional endpoints included severe respiratory exacerbations and SCS use.</p><p><strong>Results: </strong>At week 24, prebronchodilator FEV₁ was significantly improved with dupilumab versus placebo (least squares mean change, 0.203 L vs 0.002 L; least squares mean treatment difference, 0.201 L; 95% confidence interval [CI], 0.08-0.33; P=0.002). The adjusted annualized severe respiratory exacerbation rate per person-year was 0.695 (95% CI, 0.35-1.36) with dupilumab and 1.551 (95% CI, 0.75-3.22) with placebo, a 55.2% reduction; nominal P=0.0627. At week 24, 71.4% of dupilumab recipients who required SCS at baseline no longer required SCS, compared with 14.3% receiving placebo. Overall safety was consistent with the known dupilumab safety profile.</p><p><strong>Conclusions: </strong>In patients with asthma and ABPA, dupilumab significantly improved lung function compared with placebo, reduced severe respiratory exacerbations, and was well tolerated.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891701","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":"Lessons learned from clinical trials of thymic stromal lymphopoietin (TSLP) inhibition.","authors":"Jonathan Corren, Larry Borish, Christopher Brightling, Joseph K Han, Emma Guttman-Yassky, Steven Ziegler, Jean Publicover, Jyotsna Gulati, Nestor Molfino, Christopher S Ambrose, Jean-Pierre Llanos, Lang Chen, Jane R Parnes, Joseph Spahn, Andrew Lindsley","doi":"10.1016/j.jaci.2026.08.022","DOIUrl":"https://doi.org/10.1016/j.jaci.2026.08.022","url":null,"abstract":"<p><p>Type 2 (T2) immune-mediated epithelial-driven diseases are characterized by dysregulated immune responses at epithelial barrier surfaces. A key mediator of these diseases is thymic stromal lymphopoietin (TSLP), an epithelial cytokine that acts as a regulator of both T2 and non-T2 inflammation. TSLP activates dendritic cells and other immune cells, promoting the release of proinflammatory cytokines, including interleukin (IL)-4, IL-5, and IL-13. Given its central role in initiating and amplifying T2 inflammation, TSLP has emerged as a promising therapeutic target in multiple epithelial-driven inflammatory diseases. Tezepelumab is a human monoclonal antibody that selectively blocks TSLP from interacting with its receptor complex, thereby interrupting this inflammatory cascade, and its study in various disease states has clarified the clinical importance of TSLP-driven inflammation. In this review, we examine preclinical and clinical evidence and enumerate the lessons learned to date regarding the role of TSLP in sustaining select T2 inflammatory diseases-specifically asthma, chronic rhinosinusitis with nasal polyps, chronic obstructive pulmonary disease, allergic rhinitis, atopic dermatitis, and chronic spontaneous urticaria. Tezepelumab is currently the only approved anti-TSLP therapy. Other TSLP-targeting agents, including ecleralimab, SHR-1905, bosakitug, verekitug, sunakiment, TAVO101, ocankitug, HBM9378, MG-ZG122, GB-0895, and solrikitug, are in clinical development.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891732","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":"Neutralizing autoantibodies against IL-1Ra in severe bacterial community-acquired pneumonia.","authors":"Sophie Trouillet-Assant, Kylian Trepat, Natalie Fadle, Priscille Franc, Alexandre Belot, David Bussy, Christoph Kessel, Xavier Duval, Florent Salvador, Kahina Saker, Anne Conrad, Willem J B van Wamel, Nicole Lemmens, Yves Gillet, Aubin Souche, Céline Dupieux, Jean-Christophe Richard, Lorenz Thurner, François Vandenesch","doi":"10.1016/j.jaci.2026.08.001","DOIUrl":"https://doi.org/10.1016/j.jaci.2026.08.001","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891661","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":"Cadherin-26 Contributes to Intraepithelial Eosinophil and Neutrophil Infiltration in Chronic Rhinosinusitis with Nasal Polyps.","authors":"Qinqin Zhang, Xiangdong Wang, Ting He, Yuan Zhang, Mengyan Zhuang, JunMing Su, Xiaoru Yu, Ying Li, Claus Bachert, Luo Zhang, Jian Jiao","doi":"10.1016/j.jaci.2026.08.018","DOIUrl":"https://doi.org/10.1016/j.jaci.2026.08.018","url":null,"abstract":"<p><strong>Background: </strong>Chronic rhinosinusitis with nasal polyps (CRSwNP) features marked infiltration of diverse inflammatory cells. Cadherin-26 (CDH26) is an adhesion molecule associated with eosinophilic inflammation, but its role in CRSwNP remains undefined.</p><p><strong>Objective: </strong>To investigate the expression, mechanisim, and function of CDH26 in CRSwNP.</p><p><strong>Methods: </strong>Bulk and single-cell RNA sequencing and immunohistochemistry of human nasal tissues profiled CDH26 expression, localization, and its association with immune cells and inflammatory pathways in CRSwNP. Nasal epithelial cells were stimulated with cytokines to examine CDH26 expression, and were transfected to evaluate CDH26's impact on JAK-STAT signaling. Adhesion and survival assays were conducted with isolated eosinophils and neutrophils. CDH26^-/- mice were used to establish a CRSwNP model to determine CDH26's role in disease development.</p><p><strong>Results: </strong>CDH26 was elevated in eosinophilic CRSwNP (ECRSwNP) compared with control and non-eosinophilic CRSwNP (NECRSwNP) and correlated with intraepithelial infiltration of both eosinophils and neutrophils. Single-cell analysis showed its epithelial localization and co-expression with IL13RA1/STAT6 in basal cells. CDH26 was induced by IL-4/IL-13 via JAK-STAT signaling and, in turn, enhanced STAT6 phosphorylation. CDH26 mediated epithelial adhesion of eosinophils and neutrophils via integrin α4 (ITGA4) and enhanced their survival in vitro. CDH26^-/- mice showed attenuated nasal polyp-like lesion formation and reduction in the infiltration of eosinophils, neutrophils, mast cells, and T cell subsets.</p><p><strong>Conclusion: </strong>CDH26 is a type 2-inducible epithelial molecule that functions as an inflammatory mediator in CRSwNP by modulating JAK-STAT signaling and promoting eosinophil and neutrophil retention, thereby linking epithelial dysfunction to sustained inflammation and may represent a potential therapeutic target.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887598","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":"The IL-9R/Arg1 pathway promotes polyamine metabolism in human airway macrophages.","authors":"Wenwu Zhang, In Su Cheon, Abigail Pajulas, Anthony L Sinn, Maya Shraddha Krishnan, Jilu Zhang, Ahmed M Abdelaal, Xin Liu, Kaitlyn G Jackson, Jayden Zhang, Karen E Pollok, Kirsten M Kloepfer, Homer L Twigg, Benjamin Gaston, W Gerald Teague, Jie Sun, Mark H Kaplan","doi":"10.1016/j.jaci.2026.08.016","DOIUrl":"https://doi.org/10.1016/j.jaci.2026.08.016","url":null,"abstract":"<p><strong>Background: </strong>Lung macrophages are central regulators of inflammatory responses in the airways and lung parenchyma. Macrophages function as conduits for cytokine function in the inflammatory milieu. We previously demonstrated that IL-9-responsive macrophages are essential for allergic lung inflammation in an arginase 1 (Arg1) pathway.</p><p><strong>Objective: </strong>Define the IL-9/Arg1/polyamine pathway in human macrophages from model systems and asthmatic patient samples.</p><p><strong>Methods: </strong>Using humanized NSG-Quad mice treated with intranasal IL-9 and patient bronchoalveolar lavage (BAL) samples, we evaluated macrophage phenotypes via flow cytometry, bulk RNA sequencing, and metabolic assays.</p><p><strong>Results: </strong>Two distinct human lung macrophage populations were defined by the expression of CD43. IL-9 promoted the expansion of IL-9R+/Arg1+ CD43- macrophages in humanized mice. In parallel, greater proportions of IL-9R+/Arg1+ CD43- macrophages were observed in asthmatic patient BAL samples compared with healthy control patients. Higher concentrations of polyamines, downstream metabolites of Arg1 function, were detected in BAL of IL-9-treated humanized mice. There were increased concentrations of polyamines in asthmatic patient BAL, compared to control samples, and concentrations were positively correlated to BAL IL-9 concentration and increases of IL-9R+ and Arg1+ CD43- macrophages.</p><p><strong>Conclusions: </strong>IL-9-responsive CD206+ CD43- macrophages alter the metabolites present in the lung milieu. These data provide evidence for an IL-9R/Arg1/polyamine lung macrophage axis that is active in asthma patients.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887642","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":"Non-communicable inflammatory skin diseases comprise clinically meaningful distinct endotypes as identified by non-hypothesized integration of phenotypic and transcriptome data.","authors":"Natalie Garzorz-Stark, Christina Hillig, Heydar Maboudi Afkham, Martin Meinel, Manja Jargosch, Peter Seiringer, Felix Lauffer, Anna C Pilz, Xixi Li, Jigyansa Mishra, Matthias Hübenthal, Stephan Weidinger, Benjamin Klein, Lam C Tsoi, Johann Gudjonsson, Curdin Conrad, Michel Gilliet, Kenji Kabashima, Fabian Theis, Carsten B Schmidt-Weber, Tilo Biedermann, Michael P Menden, Stefanie Eyerich, Kilian Eyerich","doi":"10.1016/j.jaci.2026.08.017","DOIUrl":"https://doi.org/10.1016/j.jaci.2026.08.017","url":null,"abstract":"<p><strong>Background: </strong>Non-communicable inflammatory skin diseases (ncISDs) comprise over 100 conditions with overlapping clinical features. Current classification systems are largely based on morphology and do not adequately reflect underlying molecular mechanisms, limiting the implementation of precision therapies.</p><p><strong>Objective: </strong>To establish a data-driven, molecular framework for stratifying ncISDs independent of conventional diagnostic categories.</p><p><strong>Methods: </strong>We integrated 727 skin transcriptomes with clinical metadata from 390 patients across 22 ncISDs and applied unsupervised and machine-learning approaches to identify molecular endotypes and develop a predictive classifier.</p><p><strong>Results: </strong>We identified thirteen distinct molecular endotypes, which segregated into two major groups: seven driven by immune response programs and six by metabolic and epidermal structural pathways. Common diseases such as psoriasis and eczema distributed across multiple endotypes, highlighting substantial molecular heterogeneity. Psoriasis-dominated endotypes showed differential responses to IL-23-, IL-17-, and TNF-targeted therapies, underscoring clinical relevance. A multi-endotype classifier achieved 81.4% accuracy and was validated in independent cohorts.</p><p><strong>Conclusion: </strong>These findings define a molecularly informed framework for disease stratification that transcends traditional diagnostic boundaries and enables more precise, mechanism-based therapeutic decision-making across inflammatory diseases.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148880518","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":"Coordinated changes in oral propionate, oral microbiota, and peripheral blood inflammatory processes during peanut oral immunotherapy.","authors":"Lingdi Zhang, Yoojin Chun, Samantha Valeiron, Galina Grishina, Tracy Lo, Julie Wang, Scott Sicherer, Supinda Bunyavanich","doi":"10.1016/j.jaci.2026.08.015","DOIUrl":"https://doi.org/10.1016/j.jaci.2026.08.015","url":null,"abstract":"<p><strong>Background: </strong>Peanut allergy is an increasingly prevalent condition without curative treatment. Oral immunotherapy (OIT) can induce desensitization, but its mechanisms are not fully understood. Administration of oral short-chain fatty acids (SCFAs) in murine models induces favorable immunomodulation that overlaps with processes observed in OIT. We hypothesized that in human populations, oral SCFA levels change during OIT and are associated with systemic downregulation of Type 2 processes.</p><p><strong>Methods: </strong>Within a clinical trial of children age 4-14 years with high-threshold peanut allergy randomized to OIT or avoidance, we profiled oral SCFA levels, the oral microbiome, and peripheral blood transcriptome over the course of OIT or avoidance. Statistical and network analyses were carried out to test our hypotheses.</p><p><strong>Results: </strong>Among the 56 children in the clinical trial with complete multi-omic profiles over the trial duration, 29 were randomized to OIT and 27 to avoidance. 100% of the participants in the OIT group achieved desensitization compared to 18.5% in the avoidance group. Oral levels of the SCFA propionate increased with OIT but not avoidance (FDR=0.042) and remained elevated with sustained unresponsiveness. Oral propionate levels positively correlated with the relative abundances of several oral microbes, including known propionate producers Prevotella spp. (r=0.47, FDR 3.75x 10-3) and Veillonella (r=0.39, FDR 1.45x10-2). Oral propionate levels negatively correlated with peripheral blood transcript expression of OIT-associated Fcγ receptors (FDR≤ 0.05), IL-4 & IL-13 signaling (FDR≤ 0.05), and neutrophil degranulation pathways (FDR≤ 0.05).</p><p><strong>Conclusions: </strong>This study raises the intriguing possibility of oral propionate serving as an important immunoregulatory bridge between local and systemic processes in peanut OIT.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov NCT03907397.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148880444","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":"Characterizing the nasal microbiome using a nasal allergen challenge model.","authors":"Sophia Linton, Calvin Sjaarda, Lubnaa Hossenbaccus, Abbie Davis, Jill Greenlaw, Katya Douchant, Jen Thiele, Sarah Garvey, Hannah Botting, Lisa M Steacy, Prameet M Sheth, Anne K Ellis","doi":"10.1016/j.jaci.2026.05.003","DOIUrl":"10.1016/j.jaci.2026.05.003","url":null,"abstract":"<p><strong>Background: </strong>The role of the nasal microbiome in allergic rhinitis (AR), particularly following direct allergen exposure using a controlled model, is incompletely understood. Understanding microbiome dynamics after allergen challenge could provide insights into AR pathophysiology.</p><p><strong>Objective: </strong>We sought to evaluate nasal microbiome changes following nasal allergen challenge (NAC) with ragweed pollen extract in participants with ragweed-induced AR compared with control participants without allergy.</p><p><strong>Methods: </strong>An out-of-season NAC was completed by 19 participants with ragweed allergy and 12 control participants without allergy. Middle meatus and adjacent nasal cavity secretions were collected at baseline and 6, 24, and 48 hours after challenge. Microbial composition was characterized using 16S ribosomal RNA sequencing. Alpha diversity was assessed using the Shannon and Chao1 indices, and beta diversity was assessed using Bray-Curtis dissimilarity with principal coordinate analysis. Ragweed pollen-specific IgE (sIgE), total IgE, and Staphylococcus aureus nasal carriage were also evaluated.</p><p><strong>Results: </strong>Nasal microbial community composition differed according to biological sex (beta diversity P = .001) and S aureus carriage (P = .015). However, allergic status and NAC exposure had no significant effect on alpha or beta diversity over time. Genus-level differences between participants with AR and control participants emerged at 24 and 48 hours after challenge (P = .028 and P = .0062), with greater relative abundance of Streptococcus and Veillonella observed in control participants. Stratification by sIgE demonstrated significant differences in microbial community structure (P = .001), with higher sIgE levels associated with increased relative abundance of Streptococcus, Rothia, Staphylococcus, Neisseria, and Delftia. Higher total IgE levels were also associated with distinct microbial community profiles.</p><p><strong>Conclusions: </strong>The nasal microbiome remained stable following acute allergen exposure despite clinical responses, whereas host factors including IgE levels, sex, and S aureus carriage were associated with differences in microbial community composition.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":"783-794"},"PeriodicalIF":11.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147948514","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":"Early intervention with secukinumab prevents epigenetic scar development in new-onset psoriasis: STEPIn mechanistic substudy results.","authors":"Johann E Gudjonsson, Katharina Bier, Swann Gaulis, Lam C Tsoi, Mathias Cardner, Mrinal K Sarkar, Anthony Coon, Christopher Cole, Jaanika Kärner, Anita Fernandez, Thomas Peters, Liv Eidsmo, Lars Iversen, Piotr Jagiello, Enrico Ferrero, Frank Kolbinger, Felix Lohmann, Curdin Conrad","doi":"10.1016/j.jaci.2026.04.028","DOIUrl":"10.1016/j.jaci.2026.04.028","url":null,"abstract":"<p><strong>Background: </strong>Psoriasis is a common chronic inflammatory skin disease characterized by recurrent flares at previously affected locations. Although biologics targeting IL-17 or IL-23 effectively suppress active disease, they rarely result in long-term remission, suggesting that clinically resolved skin retains molecular changes predisposing to relapse.</p><p><strong>Objective: </strong>The STEPIn main study indicated that early intervention with secukinumab, an anti-IL-17A monoclonal antibody, may modify the course of psoriasis. This mechanistic substudy sought to define cellular and molecular changes in psoriatic skin lesions during treatment.</p><p><strong>Methods: </strong>Psoriatic skin was sampled at baseline and at up to 52 weeks of secukinumab treatment in new-onset (≤1 year) and long-standing (≥5 years) cohorts. Biopsy samples were evaluated histologically by immune profiling, global gene expression, and genome-wide DNA CpG methylation analyses.</p><p><strong>Results: </strong>Treatment with secukinumab resulted in marked molecular differences between new-onset and long-standing psoriasis despite similar clinical improvement. Gene expression normalized faster in new-onset disease but ultimately resolved in both cohorts. In contrast, disease-associated CpG methylation detected at baseline persisted despite treatment, but only in long-standing psoriasis. Baseline methylation differences were enriched for AP-1 transcription factor binding sites in long-standing disease and persistent methylation changes mapped to genes enriched for small GTPase pathways. Notably, AP-1 components were found to amplify IL-17A and TNF-α responses in keratinocytes, and a subset of these persistent methylation sites overlapped with accessible chromatin regions in psoriatic keratinocytes.</p><p><strong>Conclusions: </strong>Early secukinumab intervention may prevent formation of an epigenetic scar that persists in long-standing psoriasis even after clinical resolution.</p><p><strong>Clinical trial registration: </strong>NCT03020199.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":"857-871"},"PeriodicalIF":11.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148030596","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}