Journal of Allergy and Clinical Immunology最新文献

{"title":"Comparative efficacy and safety of treatments for eosinophilic esophagitis: Systematic review and network meta-analysis of randomized controlled trials.","authors":"Yetiani Roldan, Isabella Silang, Daniel Rayner, Vanessa Wong, Alexandro W L Chu, Nazmul Islam, Michael M Cyr, Ted Xenodemetropoulos, Matthew A Rank, Mary Sherlock, Scott H Sicherer, Hugh A Sampson, Kirsi M Järvinen, Phillippe Bégin, Jay Lieberman, R Sharon Chinthrajah, Shahzad Mustafa, Sally Joo Bailey, Anita Chandra-Puri, Patricia C Fulkerson, Ellen M McCabe, Jonathan S Tam, Marion Groetch, Maria Crain, Henry Bernstein, Kelly Cleary, Melanie Carver, Lynda Mitchell, Jennifer Gerdts, Zachary Brunet, Matthew Greenhawt, Aikaterini Anagnostou, Marcus Shaker, Julie Wang, Derek K Chu","doi":"10.1016/j.jaci.2026.09.031","DOIUrl":"https://doi.org/10.1016/j.jaci.2026.09.031","url":null,"abstract":"<p><strong>Background: </strong>Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease characterized by esophageal dysfunction and eosinophilic inflammation. Comparative efficacy and safety of therapies remain uncertain.</p><p><strong>Objective: </strong>To compare efficacy and safety of treatments for EoE in children and adults.</p><p><strong>Methods: </strong>We conducted a systematic review and network meta-analysis (NMA) of randomized controlled trials (RCTs) comparing pharmacologic, dietary, and mechanical interventions. We searched MEDLINE, EMBASE, and CENTRAL to March 17, 2026. Reviewers screened studies, extracted data, and assessed risk of bias. We conducted random-effects NMA; assessed certainty using GRADE.</p><p><strong>Results: </strong>We included 48 RCTs (3,963 participants). High-frequency dupilumab [mean difference (MD) -11.08, 95% confidence interval (CI) -15.14 to -7.03; high certainty] and swallowed topical corticosteroids (STCs) (MD -6.86, 95%CI -9.17 to -4.56; moderate certainty) are likely among the most effective for symptoms. Similarly, high-frequency dupilumab (MD 6.57, 95%CI 3.42 to 9.71; moderate certainty) and STCs (MD 7.20, 95%CI 1.01 to 13.39; moderate certainty) are among the most effective for quality-of-life. Certain biologics and epicutaneous immunotherapy are likely not different from placebo for symptoms (moderate certainty). Multiple interventions reduce peak eosinophil counts (high certainty) and likely do not increase harms versus placebo (moderate or high certainty). Four- and six-food elimination diets (FEDs) may be better than 1FED for symptoms (low certainty), but not other outcomes, with greater burden.</p><p><strong>Conclusions: </strong>High-frequency dupilumab and STCs are among the most effective therapies across patient-important and inflammatory outcomes. Histologic improvements do not guarantee patient-important outcome improvement. FED benefits are modest and low certainty, and traded off by burdens.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228000","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":"Beyond the airways: expiratory pulmonary vascular retention and reduced compressibility in asthma.","authors":"Rory Chan, Benjamin J Pippard, John V Fahy","doi":"10.1016/j.jaci.2026.10.002","DOIUrl":"https://doi.org/10.1016/j.jaci.2026.10.002","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149227984","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":"IFN-γ-NOD2/IL-5-FCGR axis enhances eosinophil extracellular trap formation in allergic bronchopulmonary aspergillosis/mycosis.","authors":"Hisashi Sasaki, Jun Miyata, Shigeharu Ueki, Yoshiki Shiraishi, Misaki Arima, Junko Suzuki, Ryuta Onozato, Yo Otsu, Emiko Matsuyama, Keeya Sunata, Yusuke Kawashima, Ryo Konno, Masaki Ishikawa, Yoshinori Hasegawa, Katsunori Masaki, Hiroki Kabata, Yoshifumi Kimizuka, Tsuyoshi Oguma, Akira Hebisawa, Akihiko Kawana, Koichiro Asano, Koichi Fukunaga","doi":"10.1016/j.jaci.2026.09.027","DOIUrl":"https://doi.org/10.1016/j.jaci.2026.09.027","url":null,"abstract":"<p><strong>Background: </strong>Allergic bronchopulmonary aspergillosis/mycosis (ABPA/M) is characterized by systemic eosinophilia and eosinophil-rich mucus plugs, but mechanisms programming eosinophil pathogenicity remain unclear.</p><p><strong>Objective: </strong>We aim to define eosinophil activation programs and upstream signals that promote extracellular trap formation in ABPA/M.</p><p><strong>Methods: </strong>We performed multi-omics analyses (RNA sequencing and proteomics) of blood eosinophils from healthy participants, patients with eosinophilic asthma, and patients with ABPA/M. Surface-marker profiles were compared between blood and airway eosinophils from patients with ABPA/M. In vitro stimulation assays using IFN-γ, IL-5, and a nucleotide-binding oligomerization domain-containing 2 (NOD2) ligand were combined with multi-omics readouts and functional evaluation of IgG cross-linking-induced eosinophil extracellular trap formation.</p><p><strong>Results: </strong>Multi-omics profiling identified activation patterns consistent with IFN-γ and IL-5 signaling in ABPA/M blood eosinophils. ICAM-1 was upregulated on both blood and airway eosinophils, whereas PD-L1 upregulation was specific to airway eosinophils. PD-L1 induction required combined stimulation with IFN-γ and a NOD2 ligand, but not IL-5. Under IFN-γ plus NOD2 ligand stimulation, eosinophils exhibited inflammatory remodeling, including increased Fc gamma receptor expression. Functionally, pretreatment with IFN-γ and a NOD2 ligand enhanced IgG cross-linking-induced extracellular trap formation in an NADPH oxidase-dependent manner and required lymphocyte function-associated antigen 1 interactions with ICAM-1. Combined stimulation with IFN-γ and IL-5 similarly augmented extracellular trap formation.</p><p><strong>Conclusion: </strong>ABPA/M eosinophils are shaped by mixed inflammatory cues, in which IFN-γ cooperates with fungal-sensing signals or IL-5 to enhance Fc gamma receptor-linked, IgG-triggered extracellular trap formation, potentially contributing to mucus plugging.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228057","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":"Type 2 Memory B Cells in Allergy: Potential Biomarkers of Allergen Immunotherapy and Novel Therapeutic Targets.","authors":"Sayuri Iwasaki, Simone Reinwald, Nicolette J T Arends, Marcus J Robinson, Robyn E O'Hehir, Menno C van Zelm","doi":"10.1016/j.jaci.2026.10.005","DOIUrl":"https://doi.org/10.1016/j.jaci.2026.10.005","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224231","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":"Lower Nasal Sphingolipids in Pediatric Asthma and Cell-Type-Specific Effects of 17q21 Variants.","authors":"Zenna Solomon, Rika Gomi, Zoe Verzani, Alan Wu, Andrea Heras, Perdita Permaul, Uthra Balaji, Jinghua Gu, Kazunori Gomi, Sarah Brown, Natalia Amos de Huerta, Natalie Gosnell, Paul Christos, Jennie G Ono, Olivier Elemento, Tilla S Worgall, Stefan Worgall","doi":"10.1016/j.jaci.2026.09.028","DOIUrl":"https://doi.org/10.1016/j.jaci.2026.09.028","url":null,"abstract":"<p><strong>Background: </strong>Genetic variations at the 17q21 asthma-risk locus regulate GSDMB and ORMDL3, influencing inflammatory pathways and sphingolipid metabolism. Although 17q21 variants such as rs7216389 and rs12936231 are associated with ORMDL3 expression in immune and airway smooth muscle cells, their effects on airway epithelial sphingolipids remain unclear.</p><p><strong>Objectives: </strong>To determine whether asthma or 17q21 asthma genotypes alter sphingolipid composition in the upper respiratory tract in children, and to define contributions of epithelial versus immune cells.</p><p><strong>Methods: </strong>Sphingolipids were quantified by mass spectrometry in nasal fluid and plasma from children with and without asthma. Nasal epithelial cells and PBMCs from healthy adults homozygous for rs7216389 C/C or T/T (risk) were analyzed for sphingolipid levels and ORMDL3/GSDMB associated gene expression.</p><p><strong>Results: </strong>Children with atopic asthma had significantly lower nasal dihydroceramides, ceramides, and sphingosine independent of inhaled corticosteroids and allergic rhinitis. Asthma was associated with increased plasma sphingolipids but decreased sphingolipids in blood cells, mirroring nasal findings. In PBMCs, the rs7216389 T allele was associated with increased ORMDL3 expression and suppressed de-novo sphingolipid synthesis. In nasal epithelial cells, the T allele predominantly increased GSDMB expression and did not alter sphingolipid metabolism.</p><p><strong>Conclusions: </strong>Nasal mucosal sphingolipids are reduced in children with atopic asthma and sphingolipids generated by de-novo sphingolipid synthesis may serve as a noninvasive biomarker of disease. 17q21 risk alleles can exert cell-type-specific effects: ORMDL3-mediated suppression of sphingolipid synthesis occurs in immune cells but not in airway epithelial cells. Systemic immune or inflammatory cell-driven alterations may contribute to reduced airway sphingolipids in asthma.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206862","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":"Comparative efficacy and safety of antihistamines, increased antihistamine dosing, and antihistamine adjuncts for chronic urticaria: a systematic review, dose-response, and network meta-analysis of randomized trials.","authors":"Alexandro W L Chu, Irene X Zhao, Daniel G Rayner, Gordon H Guyatt, Ming Liu, Cen Gao, Layla Bakaa, Paul Oykhman, Lina Chen, Paul Tran, David M Lang, Jeffrey Chan, Moshe Ben-Shoshan, Susan Waserman, Anne M Holbrook, Winfred T Frazier, Sameer K Mathur, Lisa A Beck, Eric T Oliver, Emily F Cole, Rachel N Asiniwasis, Kathryn P Trayes, Diane R Baker, David A Khan, Javed Sheikh, Lauren Runyon, Kathryn E Wheeler, Sanaz Eftekhari, Donna D Gardner, Tonya Winders, Maisie Flindall, Jamie Tattrie, Jonathan A Bernstein, Sarbjit S Saini, Derek K Chu","doi":"10.1016/j.jaci.2026.09.030","DOIUrl":"https://doi.org/10.1016/j.jaci.2026.09.030","url":null,"abstract":"<p><strong>Background: </strong>Chronic urticaria is a common immune-mediated condition characterized by wheals (itch and hives), angioedema, or both, lasting for greater than six weeks. It is managed with H1 antihistamines as the first-line therapy. Fundamental unresolved questions remain regarding the comparative benefits and harms of antihistamines and their adjuncts, and of H1 antihistamine dose-escalation.</p><p><strong>Objective: </strong>To analyze the comparative benefits and harms of antihistamines and their adjuncts (H2 blockers or montelukast), and of H1 antihistamine dose-escalation.</p><p><strong>Methods: </strong>As part of updating the American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters Chronic Urticaria guidelines, we searched MEDLINE, EMBASE, CENTRAL, and regulatory databases from inception to March 17, 2025, for randomized trials addressing antihistamines or their adjuncts for chronic urticaria. Paired reviewers independently screened records, extracted data, and assessed risk of bias. Random effects network and dose-response meta-analyses addressed urticaria activity (composed of itch and wheal scores), angioedema activity, urticaria-related quality of life, and harms including sedation. The GRADE approach informed certainty of evidence ratings.</p><p><strong>Prospero: </strong>CRD42022367280.</p><p><strong>Results: </strong>211 trials (22,187 participants) evaluated 55 unique treatments. Bilastine, desloratadine, fexofenadine, and levocetirizine are among the most effective in improving overall urticaria activity, urticaria-related quality of life, and sleep disturbance. Cetirizine and loratadine are among the most effective in reducing overall urticaria activity and its subcomponents, with cetirizine also among the most effective in improving urticaria-related quality of life. Escalating from a single to quadruple daily dose may yield diminishing additional benefit. Second-generation agents as a class may be more effective than first-generation agents in improving urticaria activity and sleep disturbance. Sedation risk likely increases with higher doses, with first-generation agents (e.g., diphenhydramine, hydroxyzine) and doxepin among the most sedating; cetirizine, ketotifen, levocetirizine, and rupatadine among the intermediate sedating; and bepotastine, bilastine, desloratadine, ebastine, fexofenadine, and loratadine among the least sedating. Adding montelukast (moderate certainty) or an H2 blocker (very low certainty) to a second-generation agent may further reduce urticaria activity.</p><p><strong>Conclusions: </strong>For chronic urticaria, second-generation agents differ in their efficacy and safety. First-generation agents are less beneficial and more harmful. Escalating to higher daily doses may provide additional benefits but likely increases sedation.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206910","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":"Allen P Kaplan, Marta Ferrer Puga, Marina Sabaté-Bresco","doi":"10.1016/j.jaci.2026.09.017","DOIUrl":"https://doi.org/10.1016/j.jaci.2026.09.017","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193858","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":"Beyond FcεRI: Rethinking endotypes in chronic spontaneous urticaria.","authors":"Zhao Wang, Songmei Geng","doi":"10.1016/j.jaci.2026.06.027","DOIUrl":"https://doi.org/10.1016/j.jaci.2026.06.027","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193825","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":"Endotypes in chronic spontaneous urticaria.","authors":"Jingwen Xue","doi":"10.1016/j.jaci.2026.06.028","DOIUrl":"https://doi.org/10.1016/j.jaci.2026.06.028","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193800","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":"Allen P Kaplan, Marta Ferrer Puga, Marina Sabaté-Bresco","doi":"10.1016/j.jaci.2026.09.018","DOIUrl":"https://doi.org/10.1016/j.jaci.2026.09.018","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193837","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}