Journal of Allergy and Clinical Immunology最新文献

{"title":"Analysis of human neutrophils from nasal polyps by single-cell RNA sequencing reveals roles of neutrophils in chronic rhinosinusitis.","authors":"Naruhito Iwasaki, Julie A Poposki, Masanori Kidoguchi, Aiko Oka, Aiko I Klingler, Whitney W Stevens, Lydia A Suh, Junqin Bai, Anju T Peters, Leslie C Grammer, Kevin C Welch, Stephanie S Smith, David B Conley, Bruce S Bochner, Robert P Schleimer, Robert C Kern, Bruce K Tan, Atsushi Kato","doi":"10.1016/j.jaci.2024.10.032","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.10.032","url":null,"abstract":"<p><strong>Background: </strong>Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by type 2 (T2) inflammation. Recent studies, including our own, suggest that neutrophils are also elevated in T2 nasal polyps (NPs) and that elevated neutrophils display an activated phenotype. However, the actual roles of neutrophils in NP pathogenesis in T2 CRSwNP are still largely unclear.</p><p><strong>Objective: </strong>To reveal the roles and heterogeneity of neutrophils in NP tissue by single cell RNA-Sequencing (scRNA-Seq) analysis.</p><p><strong>Methods: </strong>We developed a novel microwell-based scRNA-Seq assay (BD Rhapsody platform) using granulocyte enriched samples from 5 control sinus tissues (CTs), 5 NP tissues and patient matched peripheral blood (PB) samples. This approach allowed for the examination of differential expression of genes in NP neutrophils by the Benjamini-Hochberg algorithm and predicted the overall function of NP neutrophils by pathway and gene ontology (GO) enrichment analyses.</p><p><strong>Results: </strong>After all QC steps, we successfully detected neutrophils. We identified 333 down-regulated and 128 up-regulated genes in NP neutrophils (1,151 cells) compared to all PB neutrophils (13,591 cells) (>1.5-fold, q<0.05), and found commonly dysregulated genes in NP neutrophils compared to both all PB and CT neutrophils (3,136 cells). Commonly down-regulated genes in NP neutrophils were associated with the innate immune system, and up-regulated genes were associated with NF-κB signaling, cytokine activity and cellular response to oxygen-containing compounds. NP neutrophils displayed 4 clusters revealing potential heterogeneity of neutrophils in NP tissue.</p><p><strong>Conclusions: </strong>Elevated neutrophils in NP tissue appear to exist in several subphenotypes that may play important pathogenic roles in CRSwNP.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620952","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":"Phase 2b randomized clinical trial of amlitelimab, an anti-OX40 ligand antibody, in patients with moderate-to-severe atopic dermatitis.","authors":"Stephan Weidinger, Andrew Blauvelt, Kim A Papp, Adam Reich, Chih-Hung Lee, Margitta Worm, Charles Lynde, Yoko Kataoka, Peter Foley, Xiaodan Wei, Wanling Wong, Anne-Catherine Solente, Christine Weber, Samuel Adelman, Sonya Davey, Fabrice Hurbin, Natalie Rynkiewicz, Karl Yen, John T O'Malley, Charlotte Bernigaud","doi":"10.1016/j.jaci.2024.10.031","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.10.031","url":null,"abstract":"<p><strong>Background: </strong>Amlitelimab, a fully human nondepleting monoclonal antibody targeting OX40 ligand on antigen-presenting cells, could prevent T-cell-driven inflammation seen in atopic dermatitis (AD).</p><p><strong>Objective: </strong>This trial evaluated the efficacy and safety of amlitelimab in adults with AD.</p><p><strong>Methods: </strong>In this 2-part, phase 2b, randomized, double-blinded placebo-controlled trial (NCT05131477), patients received subcutaneous amlitelimab every 4 weeks at doses of 250 mg with 500-mg loading dose, 250 mg, 125 mg, or 62.5 mg, or placebo for 24 weeks in Part 1 (1:1:1:1:1 randomization). In Part 2, clinical responders were reallocated 3:1 to withdraw amlitelimab or continue the previous dose regimen for 28 weeks. The primary end point was percent change in Eczema Area and Severity Index (EASI) from baseline to Week 16.</p><p><strong>Results: </strong>390 and 190 patients enrolled in Part 1 and Part 2, respectively. Significant percent change decreases in EASI were observed with amlitelimab vs. placebo (P<.001). Clinical responses at Week 24 (Investigator Global Assessment 0/1 and/or EASI-75) were maintained at Week 52 in patients continuing or withdrawn from amlitelimab. In patients maintaining clinical response at Week 52 while off-treatment, >80% had serum amlitelimab concentrations below a 4-μg/mL threshold for several weeks prior to Week 52. Reductions in AD-related biomarkers during Part 1 were maintained through Part 2. Amlitelimab was well tolerated over 52 weeks.</p><p><strong>Conclusions: </strong>Amlitelimab treatment significantly reduced clinical and biomarker responses, and was well tolerated in adults with AD through Week 52. Sustained responses were observed in the majority of patients after amlitelimab withdrawal for 28 weeks.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620988","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":"Profiling immune cell tissue niches in the spatial \"omics\" era.","authors":"Colin Yc Lee, James McCaffrey, Dominic McGovern, Menna R Clatworthy","doi":"10.1016/j.jaci.2024.11.001","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.11.001","url":null,"abstract":"<p><p>Immune responses require complex, spatially-coordinated interactions between immune cells and their tissue environment. For decades, we have imaged tissue sections to visualise a limited number of immune-related macromolecules in situ, functioning as surrogates for cell types or processes of interest. However, this inevitably provides a limited snapshot of the tissue's immune landscape. Recent developments in high-throughput spatial \"omic\" technologies, particularly spatial transcriptomics, and its application to human samples has facilitated a more comprehensive understanding of tissue immunity, by mapping fine-grained immune cell states to their precise tissue location, while providing contextual information about their immediate cellular and tissue environment. These data provide opportunities to investigate mechanisms underlying the spatial distribution of immune cells and its functional implications, including the identification of \"immune niches\", although the criteria used to define this term have been inconsistent. Here, we review recent technological and analytical advances in multi-parameter spatial profiling, focussing on how these methods have generated new insights in translational immunology. We propose a 3-step framework for the definition and characterisation of immune niches, which is powerfully facilitated by new spatial profiling methodologies. Finally, we summarise current approaches to analyse adaptive immune repertoires and lymphocyte clonal expansion in a spatially-resolved manner.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620992","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":"Pedro A Lamothe, Martin C Runnstrom, F Eun-Hyung Lee","doi":"10.1016/j.jaci.2024.10.003","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.10.003","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620998","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":"Impact of biologics on the immune response to mRNA COVID-19 vaccination in patients with asthma.","authors":"Shu-Yi Liao, Barry Make, Michael E Wechsler","doi":"10.1016/j.jaci.2024.09.028","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.09.028","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620974","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":"Booster vaccination normalizes postvaccination immunity in patients with severe asthma.","authors":"Hitasha Rupani, Rekha Chaudhuri, David J Jackson, Helen Moyses, Ramesh J Kurukulaaratchy, Hans Michael Haitchi, Michael R Edwards, Sebastian L Johnston, Ratko Djukanovic","doi":"10.1016/j.jaci.2024.09.027","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.09.027","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620967","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":"Implementation of the esophageal string test in clinical practice and research.","authors":"Shauna Schroeder, Cindy S Bauer, Benjamin L Wright","doi":"10.1016/j.jaci.2024.11.002","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.11.002","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620976","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":"Prevalence and outcomes of cancer and treatment-associated toxicities for patients with Ataxia Telangiectasia.","authors":"Aimee Magnarelli, Qi Liu, Fan Wang, Xiao Peng, Jennifer Wright, Ninad Oak, Valerie Natale, Cynthia Rothblum-Oviatt, Maureen A Lefton-Greif, Sharon McGrath-Morrow, Thomas O Crawford, Matthew J Ehrhardt, Howard M Lederman, Richa Sharma","doi":"10.1016/j.jaci.2024.10.023","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.10.023","url":null,"abstract":"<p><strong>Background: </strong>Ataxia Telangiectasia (A-T) is a DNA repair disorder with cancer predisposition.</p><p><strong>Objective: </strong>Characterize the prevalence and outcomes of hematologic and solid cancers and treatment-associated toxicities in individuals with A-T.</p><p><strong>Methods: </strong>Data was retrospectively analyzed from the Johns Hopkins Ataxia Telangiectasia Clinical Center cohort. Cumulative incidence and standardized incidence ratios of cancer, survival probability after cancer diagnosis, and standardized mortality ratios were calculated. Cox regression estimated risk of death based on chemotherapy (standard v reduced) dosing and multivariable logistic regression evaluated cancer risk associations with ATM exons and variants.</p><p><strong>Results: </strong>Eighty-four (16.5%) of 508 individuals were diagnosed with a primary cancer, 62 (74%) were hematologic in origin and 22 (26%) were solid organ cancers. The cumulative incidence of cancer was 29% by age 35 years. Non-Hodgkin lymphoma occurred most frequently (n=39), while solid cancers disproportionately affected those ≥18 years old (n=22). The standardized mortality ratio was 24.6 (95% CI:21.1-28.4) overall and 232.9 (95% CI:178.1-299.2) among individuals with cancer. Risk of death was higher when treated with standard/unknown versus modified chemotherapy (HR 2.2, 95% CI:1.1-4.4, p=0.024). Chemotherapy-associated toxicities developed in 58% of individuals, predominantly neurologic (n=14) and gastrointestinal (n=10) systems. Three exons were enriched for cancer-associated variants.</p><p><strong>Conclusion: </strong>Individuals with A-T experience a wide array of blood and solid organ malignancies, high mortality rates, and treatment related toxicities, highlighting need for targeted therapies to mitigate toxicity and optimize survival.</p><p><strong>Clinical implication: </strong>A-T patients with cancer face elevated mortality rates, underscoring the urgency for tailored therapies to minimize toxicity and improve survival outcomes.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620990","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":"Effect of Mepolizumab in airway's remodelling in patients with late-onset severe asthma with an eosinophilic phenotype.","authors":"Kalliopi Domvri, Ioanna Tsiouprou, Petros Bakakos, Paschalis Steiropoulos, Konstantinos Katsoulis, Konstantinos Kostikas, Katerina M Antoniou, Andriana I Papaioannou, Nikoletta Rovina, Paraskevi Katsaounou, Theodora Papamitsou, Nicoleta Pastelli, Stavros Tryfon, Evangelia Fouka, Despoina Papakosta, Stelios Loukides, Konstantinos Porpodis","doi":"10.1016/j.jaci.2024.10.024","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.10.024","url":null,"abstract":"<p><strong>Background: </strong>Clinical trials and real-world experience have provided evidence for the clinical benefit of mepolizumab, an anti-IL-5 biologic, in severe asthma. However, limited data exists regarding the impact of mepolizumab on airway remodelling.</p><p><strong>Objective: </strong>We thus investigated the effect of mepolizumab on airway structural remodelling in patients treated for severe asthma in routine clinical care.</p><p><strong>Methods: </strong>MESILICO is a multicenter study involving 8 Pulmonology Departments in Greece. This study focused on patients who initiated mepolizumab for severe asthma with an eosinophilic phenotype and had late-onset disease with obstructive patterns (impaired reversibility). Forty-seven patients were recruited, of whom 41 were enrolled in the bronchoscopy sub-study. The findings were related to clinical outcome.</p><p><strong>Results: </strong>After 12 months, mepolizumab treatment was associated with significant improvements in lung function and ACT score, along with a significant decrease in severe exacerbation events (p<0.001). Thirty four of the 41 participants (83%) had paired biopsies for comparative analysis. There was a significant reduction from baseline in sub-basement membrane thickness, airway smooth muscle area, airway smooth muscle layer thickness and extent of epithelial damage, as well as a decrease in tissue eosinophil numbers (all p<0.001). The extent of ASMLT reduction positively correlated with the submucosal eosinophil reduction (r= 0.599, p<0.001).</p><p><strong>Conclusion: </strong>This study identifies that 12 month of mepolizumab treatment in patients with late-onset severe asthma, who are also characterized by eosinophilic and impaired reversibility phenotypes, leads not only to clinical improvement but also reduces indices of airway tissue remodelling suggestive of a disease modifying effect.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620970","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":"Unravelling the noise in pharmacokinetic studies of epinephrine: time to focus on cardiac output?","authors":"Nandinee Patel, Lucy Hawkins, Paul J Turner","doi":"10.1016/j.jaci.2024.10.026","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.10.026","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621013","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}