Patrick K Gleeson,Knashawn H Morales,Hannah J Lee,Olajumoke O Fadugba,Priya J Patel,Audreesh Banerjee,Andrea J Apter,Jason D Christie,Meeta Prasad Kerlin
{"title":"Guideline adherence to aeroallergen-focused activities in adult asthma care: Insights from an online survey.","authors":"Patrick K Gleeson,Knashawn H Morales,Hannah J Lee,Olajumoke O Fadugba,Priya J Patel,Audreesh Banerjee,Andrea J Apter,Jason D Christie,Meeta Prasad Kerlin","doi":"10.1016/j.jaci.2025.09.013","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.09.013","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"2 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145261306","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":"Promising results of β-blockers in the spectrum of aquagenic urticaria, cholinergic urticaria, and adrenergic urticaria.","authors":"Evelien Hutten,Inger Bocca-Tjeertes,Rick Pleijhuis","doi":"10.1016/j.jaci.2025.09.007","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.09.007","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"7 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145261530","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":"Reply.","authors":"Jonathan A Bernstein","doi":"10.1016/j.jaci.2025.09.008","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.09.008","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.2,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274767","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}
Nadia Baalbaki,Daniëlle van Egmond,Patricia Jaeger,Merel E B Cornelissen,Sien T Verbeek,Milena Sokolowska,Cornelis M van Drunen,Anke H Maitland-van der Zee,Korneliusz Golebski,
{"title":"Barrier dysfunction in nasal epithelium contributes to persistent inflammation in long COVID.","authors":"Nadia Baalbaki,Daniëlle van Egmond,Patricia Jaeger,Merel E B Cornelissen,Sien T Verbeek,Milena Sokolowska,Cornelis M van Drunen,Anke H Maitland-van der Zee,Korneliusz Golebski, ","doi":"10.1016/j.jaci.2025.09.024","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.09.024","url":null,"abstract":"RATIONALE AND OBJECTIVESLong COVID (LC) is characterized by persistent symptoms associated with chronic inflammation and immune dysregulation, but the local tissue mechanisms driving these processes remain poorly understood. Given that the nasal epithelium is the primary entry and infection site for SARS-CoV-2, we aimed to investigate its role in LC and its potential contribution to systemic immune activation.METHODSWe analyzed nasal epithelial samples and peripheral blood from participants in the Precision Medicine for more Oxygen (P4O2) COVID-19 cohort, post-COVID individuals and healthy controls. We assessed epithelial barrier integrity, evaluated wound healing and explored cytokine profiles. Transcriptomic analysis was performed via RNA-sequencing. Blood innate lymphoid cells (ILCs) were phenotyped by flow cytometry and stimulated in vitro for functional assays.RESULTSAmong a subgroup of LC patients, nasal epithelial cells showed impaired barrier function, reduced expression of ZO-1 and occludin and exaggerated sensitivity to viral triggers. Despite faster wound closure, the epithelial repair was reduced. The LC nasal epithelium exhibited increased cytokine production, including IL-1β and transcriptomic signatures of inflammation, including upregulation of interferon pathways. Furthermore, we found that TFs ATF3 and EGR1 were downregulated in LC. Elevated IL-1β levels in nasal epithelium promoted ILC activation and plasticity towards IFN-γ-producing ILCs in blood.CONCLUSIONWhile multiple organ systems are implicated in LC, our findings identified nasal epithelial dysfunction in a subgroup of LC patients and chronic activation as potential contributors to systemic immune dysregulation. The IL-1β-IFN-γ axis represents a novel targetable pathway that may support precision therapies for long COVID.","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"28 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145261302","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":"Selective IL-2 delivery modulates CD8+ T cells in human HLH and ameliorates disease features in a murine model.","authors":"Tommaso Marchetti,Samantha Milanesi,Diana Tintor,Julius Köppen,Tiziana Lorenzini,Severin Walser,Stefano Vavassori,Onur Boyman,Jana Pachlopnik Schmid","doi":"10.1016/j.jaci.2025.09.009","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.09.009","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"9 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145246600","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}
Aiko Oka,Aiko I Klingler,Masanori Kidoguchi,Julie A Poposki,Lydia A Suh,Junqin Bai,Whitney W Stevens,Anju T Peters,Leslie C Grammer,Kevin C Welch,Stephanie S Smith,David B Conley,Brian S Schwartz,Micah Johnson,Amr Radwan,Robert P Schleimer,Robert C Kern,Bruce K Tan,Shigeharu Fujieda,Mitsuhiro Okano,Atsushi Kato
{"title":"Effects of type 3 and neutrophilic inflammation on type 2 chronic rhinosinusitis with nasal polyps.","authors":"Aiko Oka,Aiko I Klingler,Masanori Kidoguchi,Julie A Poposki,Lydia A Suh,Junqin Bai,Whitney W Stevens,Anju T Peters,Leslie C Grammer,Kevin C Welch,Stephanie S Smith,David B Conley,Brian S Schwartz,Micah Johnson,Amr Radwan,Robert P Schleimer,Robert C Kern,Bruce K Tan,Shigeharu Fujieda,Mitsuhiro Okano,Atsushi Kato","doi":"10.1016/j.jaci.2025.09.023","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.09.023","url":null,"abstract":"BACKGROUNDChronic rhinosinusitis with nasal polyps (CRSwNP) is most commonly divided into 3 endotypes, type 1 (T1), T2 and T3 based on the T cell cytokine profiles. While neutrophils are classically associated with T3 inflammation in CRS, neutrophilic infiltration can be present without a T3 signal.OBJECTIVEWe sought to identify the effects of T3 and neutrophilic (called neutrophil variant or Vneut) inflammation on clinical presentations and phenotype-associated mechanisms in patients with T2 CRSwNP.METHODSWe obtained 66 control ethmoid tissues and 158 nasal polyps (NPs). We measured mRNA markers for T1, T2, T3 and Vneut inflammation by quantitative RT-PCR, and whole RNA expression profiles by bulk RNA-Sequencing. We investigated associations between the endotypes and natural histories and predicted molecular pathways by gene enrichment analysis.RESULTSSince 96% of the NPs had T2 endotype, most T1, T3 and Vneut coexisted with T2 endotype. Recurrent NP was associated with both T2+T3 (p=0.012) and T2+Vneut (p=0.022) mixed inflammation, while sinus CT and NP scores were only associated with T2+Vneut inflammation (p<0.05). Compared to control tissues, we identified shared and specific dysregulated genes in T2-single, T2+T3 and T2+Vneut mixed endotypes, and the results suggest that NP recurrence (T2+T3 and T2+Vneut shared dysregulated genes) was associated with activation of cytotoxic T cells and M1 macrophages, while sinus CT and NP scores (T2+Vneut-specific genes) were associated with activation of neutrophils, M2 macrophages and fibroblasts as well as down-regulation of innate host defense.CONCLUSIONST3 and neutrophilic inflammation induce different molecular pathways resulting in distinct clinical presentations in T2 CRSwNP.","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"28 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145254764","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}
Julie M Caldwell,Adina Y Ballaban,Jie Li,Rachel Maddux,Sarah Harris,Evan S Dellon,Marc E Rothenberg
{"title":"Cendakimab (Anti-IL-13) administration improves esophageal gene expression in eosinophilic esophagitis.","authors":"Julie M Caldwell,Adina Y Ballaban,Jie Li,Rachel Maddux,Sarah Harris,Evan S Dellon,Marc E Rothenberg","doi":"10.1016/j.jaci.2025.08.032","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.08.032","url":null,"abstract":"BACKGROUNDIL-13 has been implicated as a key contributor to the pathogenesis of eosinophilic esophagitis (EoE) based in part on the finding that cendakimab (a humanized monoclonal anti-IL-13 antibody) significantly improved esophageal eosinophils, endoscopic severity, histology grade and stage, and clinician's assessment of severity in the HEROES phase 2 trial.OBJECTIVEWe aimed to determine how cendakimab administration impacted esophageal gene expression in the HEROES phase 2 trial (NCT02098473).METHODSEoE-related transcripts were quantified in biopsies collected at baseline (week 0) and after 16 weekly injections (week 16) of cendakimab (180 mg or 360 mg) or placebo. Genes exhibiting differential expression after cendakimab treatment were identified. Esophageal gene expression pre- and post-treatment in histologic and endoscopic responders and non-responders was compared. Additionally, we assessed whether esophageal gene expression correlated with histologic and endoscopic parameters.RESULTSCompared with placebo, cendakimab (at both doses) reversed the gene expression profiles of cardinal genes and molecular pathways involved in EoE pathogenesis. These changes included genes involved in IL-13 signaling (eg, CCL26), mastocytosis (eg, CPA3, TPSB2/TPSAB1), epithelial differentiation (eg, DSG1), and remodeling (eg, POSTN). Transcript changes correlated with histologic and endoscopic observations. Patients who did not achieve histologic remission still demonstrated improved post-treatment transcript expression, although patients who achieved histologic remission exhibited greater improvement in post-treatment expression in a subset of genes than did patients who did not achieve histologic remission. Both endoscopic responders and non-responders exhibited improvement in post-treatment expression.CONCLUSIONCendakimab treatment normalizes the aberrant esophageal gene expression seen in patients with EoE, and the changes in transcripts correlate with histologic and endoscopic improvements. The finding that cendakimab corrects esophageal transcript expression even in endoscopic non-responders suggests that the IL-13 pathway is driving EoE pathogenesis in most patients. These collective findings, derived from a multisite, double-blinded, placebo-controlled trial, add molecular evidence that IL-13 drives EoE pathogenesis.","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"90 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145254763","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 diagnostic pitfall of sIL-2R in hemophagocytic lymphohistiocytosis: A key marker lost in analytic translation.","authors":"Josia Fauser,Werner Klotz,Manuel Trebo,Andreas Pircher,Sieghart Sopper,Dominik Wolf,Günter Weiss,David Haschka","doi":"10.1016/j.jaci.2025.09.005","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.09.005","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"45 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145215834","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":"Lifestyle-associated metabolite signatures and the risk of late-onset asthma.","authors":"Qinyu Chang,Lu Chen,Yiqun Zhu,Ben Liu,Xin Zhou,Huaying Liang,Fengyu Lin,Dianwu Li,Zhuanxing Zhu,Zhaojun Pan,Xiang Chen,Hong Liu,Dianjianyi Sun,Jun Lv,Liming Li,Pinhua Pan,Canqing Yu,Yan Zhang, ","doi":"10.1016/j.jaci.2025.09.020","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.09.020","url":null,"abstract":"BACKGROUNDUnhealthy lifestyle behaviors, leading to systemic metabolic disturbances, are significantly linked to the risk of late-onset asthma. However, the underlying metabolism-related mechanisms remain unclear.OBJECTIVEThis study aims to identify lifestyle-related metabolites and assess their predictive value for incident asthma.METHODSUsing NMR metabolomics data from the UK Biobank population (aged 40-69), plasma metabolites associated with healthy lifestyle scores were identified through multiple linear regression. Cox proportional hazards regression was used to further screen metabolites linked to late-onset asthma risk. Elastic net regularization selected critical metabolites for developing an asthma risk prediction model, incorporating conventional clinical characteristics and lifestyle factors. A metabolic score based on non-zero regularization coefficients was derived, and its association with asthma risk was evaluated through survival analysis. Models and metabolic score performance were validated in unused internal UK Biobank participants and an external China Kadoorie Biobank cohort.RESULTSAmong 198,607 participants (mean age 56.4 years), 159 plasma metabolites were significantly related to healthy lifestyle scores, 103 of which were associated with incident asthma risk. Nine metabolites were selected and incorporated into the asthma risk prediction model, significantly improving its predictive performance (Area under the curve: 0.812 vs. 0.758). Individuals with an unfavorable metabolic signature exhibited a 77.0% increased risk (hazard ratio [HR] 1.770, 95% confidence interval [CI] 1.634-1.918) of developing asthma compared to those with a favorable metabolic signature, with a stronger effect observed in females (HR 1.914, 95% CI 1.729-2.118). The results for the predictive model and metabolic score were confirmed in both internal and external validations.CONCLUSIONMultiple lifestyle-related metabolites are associated with late-onset asthma risk and can help stratify asthma risk, particularly among females.","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"27 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145229222","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}