Journal of Allergy and Clinical Immunology最新文献

{"title":"Is there a role for vitamin supplementation in pollutant-related childhood asthma?","authors":"Allen Joe MD , Yueh-Ying Han PhD , Franziska J. Rosser MD, MPH , Augusto A. Litonjua MD, MPH , Juan C. Celedón MD, DrPH, FAAAAI","doi":"10.1016/j.jaci.2025.01.012","DOIUrl":"10.1016/j.jaci.2025.01.012","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 4","pages":"Pages 1196-1198"},"PeriodicalIF":11.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023411","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 role of mitochondrial DNA copy number in asthma: Agent or bystander?","authors":"Anurag Agrawal MBBS, PhD , Ira Agrawal , George Davey Smith MD, DSc, MSc","doi":"10.1016/j.jaci.2025.01.023","DOIUrl":"10.1016/j.jaci.2025.01.023","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 4","pages":"Pages 1202-1204"},"PeriodicalIF":11.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074496","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":"Mitochondrial DNA copy number variation in asthma risk, severity, and exacerbations","authors":"Weiling Xu MD ,&nbsp;Yun Soo Hong MD, PhD ,&nbsp;Bo Hu PhD ,&nbsp;Suzy A.A. Comhair PhD ,&nbsp;Allison J. Janocha BS ,&nbsp;Joe G. Zein MD, PhD ,&nbsp;Ruoying Chen PhD ,&nbsp;Deborah A. Meyers PhD ,&nbsp;David T. Mauger PhD ,&nbsp;Victor E. Ortega MD, PhD ,&nbsp;Eugene R. Bleecker MD ,&nbsp;Mario Castro MD ,&nbsp;Loren C. Denlinger MD, PhD ,&nbsp;John V. Fahy MD ,&nbsp;Elliot Israel MD ,&nbsp;Bruce D. Levy MD ,&nbsp;Nizar N. Jarjour MD ,&nbsp;Wendy C. Moore MD ,&nbsp;Sally E. Wenzel MD ,&nbsp;Benjamin Gaston MD ,&nbsp;Serpil C. Erzurum MD","doi":"10.1016/j.jaci.2024.08.022","DOIUrl":"10.1016/j.jaci.2024.08.022","url":null,"abstract":"<div><h3>Background</h3><div>Asthma pathophysiology is associated with mitochondrial dysfunction. Mitochondrial DNA copy number (mtDNA-CN) has been used as a proxy of mitochondrial function, with lower levels indicating mitochondrial dysfunction in population studies of cardiovascular diseases and cancers.</div></div><div><h3>Objectives</h3><div>We investigated whether lower levels of mtDNA-CN are associated with asthma diagnosis, severity, and exacerbations.</div></div><div><h3>Methods</h3><div>mtDNA-CN is evaluated in blood from 2 cohorts: UK Biobank (UKB) (asthma, n = 39,147; no asthma, n = 302,302) and Severe Asthma Research Program (SARP) (asthma, n = 1283; nonsevere asthma, n = 703).</div></div><div><h3>Results</h3><div>Individuals with asthma have lower mtDNA-CN compared to individuals without asthma in UKB (beta, −0.006 [95% confidence interval, −0.008 to −0.003], <em>P</em> = 6.23 × 10⁻⁶). Lower mtDNA-CN is associated with asthma prevalence, but not severity in UKB or SARP. mtDNA-CN declines with age but is lower in individuals with asthma than in individuals without asthma at all ages. In a 1-year longitudinal study in SARP, mtDNA-CN was associated with risk of exacerbation; those with highest mtDNA-CN had the lowest risk of exacerbation (odds ratio 0.333 [95% confidence interval, 0.173 to 0.542], <em>P</em> = .001). Biomarkers of inflammation and oxidative stress are higher in individuals with asthma than without asthma, but the lower mtDNA-CN in asthma is independent of general inflammation or oxidative stress. Mendelian randomization studies suggest a potential causal relationship between asthma-associated genetic variants and mtDNA-CN.</div></div><div><h3>Conclusion</h3><div>mtDNA-CN is lower in asthma than in no asthma and is associated with exacerbations. Low mtDNA-CN in asthma is not mediated through inflammation but is associated with a genetic predisposition to asthma.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 4","pages":"Pages 1224-1235"},"PeriodicalIF":11.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140132","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":"Targeting of the IL-5 pathway in severe asthma reduces mast cell progenitors","authors":"P. Abigail Alvarado-Vazquez PhD ,&nbsp;Erika Mendez-Enriquez PhD ,&nbsp;Maya Salomonsson PhD ,&nbsp;Peter Kopac MD, PhD ,&nbsp;Ana Koren PhD ,&nbsp;Urska Bidovec-Stojkovic PhD ,&nbsp;Sabina Škrgat MD, PhD ,&nbsp;Oscar E. Simonson MD, PhD ,&nbsp;Valentyna Yasinska MD, PhD ,&nbsp;Sven-Erik Dahlén MD, PhD ,&nbsp;Gunnar Pejler PhD ,&nbsp;Christer Janson MD, PhD ,&nbsp;Peter Korosec PhD ,&nbsp;Andrei Malinovschi MD, PhD ,&nbsp;Jenny Hallgren PhD","doi":"10.1016/j.jaci.2024.10.025","DOIUrl":"10.1016/j.jaci.2024.10.025","url":null,"abstract":"<div><h3>Background</h3><div>Therapies targeting IL-5 or its receptor (IL-5Rα) are currently used to treat patients with severe eosinophilic asthma.</div></div><div><h3>Objective</h3><div>We sought to investigate the impact of anti–IL-5 and anti–IL-5Rα biological therapies on mast cells (MCs) and their progenitors.</div></div><div><h3>Methods</h3><div>Surface IL-5Rα expression was investigated on MCs and their progenitors in mouse lungs and bone marrow and in human lungs and blood. Isolated human MC progenitors cultured in the presence or absence of IL-5 were analyzed <em>in vitro</em>. Circulating MC progenitors were quantified in patients with severe asthma before and after anti–IL-5 (mepolizumab) or anti–IL-5Rα (benralizumab) therapy. Gene expression analysis of MC progenitors was performed before and after anti–IL-5Rα therapy.</div></div><div><h3>Results</h3><div>Approximately 50% of the human primary lung MCs and 30% of the human MC progenitors from individuals with allergic asthma expressed IL-5Rα. In patients with mild to moderate allergic asthma and mice with acute allergic airway inflammation, the fraction of IL-5Rα⁺ MC progenitors was elevated. In addition, IL-5 promoted the proliferation and/or survival of isolated human MC progenitors. Furthermore, patients with severe asthma from 2 independent cohorts demonstrated a reduction in blood MC progenitors after anti–IL-5 or anti–IL-5Rα treatment. This was associated with improved asthma control as well as a decline in both blood eosinophils and T_H2 cells. Finally, the blood MC progenitors remaining after anti–IL-5Rα (benralizumab) treatment exhibited a downregulated expression of genes involved in growth and proliferation.</div></div><div><h3>Conclusions</h3><div>This study introduces the possibility that the clinical effects of targeting IL-5/IL-5Rα in severe asthma may also involve reduction of MC populations.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 4","pages":"Pages 1310-1320"},"PeriodicalIF":11.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621004","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}

{"title":"Update on mast cell biology","authors":"Hadas Tamar Pahima PhD ,&nbsp;Daniel F. Dwyer PhD","doi":"10.1016/j.jaci.2024.12.1092","DOIUrl":"10.1016/j.jaci.2024.12.1092","url":null,"abstract":"<div><div>Mast cells (MCs) are heterogeneous tissue-resident effector cells that are thought to play central roles in allergic inflammatory disease, yet the degree of heterogeneity and nature of these roles has remained elusive. In recent years, advances in tissue culture systems, preclinical mouse models, and the continued spread of single-cell RNA sequencing have greatly advanced our understanding of MC phenotypes in health and disease. These approaches have identified novel interactions of MC subsets with immune cells, neurons, and tissue structural cells, changing our understanding of how MCs both drive and help resolve tissue inflammation, reshape tissue microenvironments, and influence host behavior. This review addresses key studies from 2022 to 2024 that have advanced our understanding of MC biology in mice and humans.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 4","pages":"Pages 1115-1123"},"PeriodicalIF":11.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970840","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":"Eosinophilic esophagitis drives tissue fibroblast regenerative programs toward pathologic dysfunction","authors":"Medet Jumabay MD, PhD ,&nbsp;Edsel M. Abud MD, PhD ,&nbsp;Kevin Okamoto BS ,&nbsp;Paramita Dutta MSc ,&nbsp;Austin W.T. Chiang PhD ,&nbsp;Haining Li MS ,&nbsp;Mario C. Manresa PhD ,&nbsp;Yanfang P. Zhu PhD ,&nbsp;Dana Frederick MS ,&nbsp;Richard Kurten PhD ,&nbsp;Ben Croker PhD ,&nbsp;Nathan E. Lewis PhD ,&nbsp;Joshua L. Kennedy MD ,&nbsp;Ranjan Dohil MD ,&nbsp;Michael Croft PhD ,&nbsp;Ferhat Ay PhD ,&nbsp;Joshua B. Wechsler MD, MS ,&nbsp;Seema S. Aceves MD, PhD","doi":"10.1016/j.jaci.2024.11.028","DOIUrl":"10.1016/j.jaci.2024.11.028","url":null,"abstract":"<div><h3>Background</h3><div>Pathologic tissue remodeling with scarring and tissue rigidity has been demonstrated in inflammatory, autoimmune, and allergic diseases. Eosinophilic esophagitis (EoE) is an allergic disease that is diagnosed and managed by repeated biopsy procurement, allowing an understanding of tissue fibroblast dysfunction. While EoE-associated tissue remodeling causes clinical dysphagia, food impactions, esophageal rigidity, and strictures, molecular mechanisms driving these complications remain under investigation.</div></div><div><h3>Objective</h3><div>We hypothesized that chronic EoE inflammation induces pathogenic fibroblasts with dysfunctional tissue regeneration and motility.</div></div><div><h3>Methods</h3><div>We used single-cell RNA sequencing, fluorescence-activated cell sorting analysis, and fibroblast differentiation and migration assays to decipher the induced and retained pathogenic dysfunctions in EoE versus healthy esophageal fibroblasts.</div></div><div><h3>Results</h3><div>Differentiation assays demonstrated that active EoE fibroblasts retain regenerative programs for rigid cells such as chondrocytes (<em>P</em> &lt; .05) but lose healthy fibroblast capacity for soft cells such as adipocytes (<em>P</em> &lt; .01), which was reflected in biopsy sample immunostaining (<em>P</em> &lt; .01). EoE, but not healthy, fibroblasts show proinflammatory and prorigidity transcriptional programs on single-cell RNA sequencing. <em>In vivo,</em> regenerative fibroblasts reside in perivascular regions and near the epithelial junction, and during EoE, they have significantly increased migration (<em>P</em> &lt; .01). Flow analysis and functional assays demonstrated that regenerative EoE fibroblasts have decreased surface CD73 expression and activity (both <em>P</em> &lt; .05) compared to healthy controls, indicating aberrant adenosine triphosphate handling. EoE fibroblast dysfunctions were induced in healthy fibroblasts by reducing CD73 activity and rescued in EoE using adenosine repletion.</div></div><div><h3>Conclusion</h3><div>A normalization of perturbed extracellular adenosine triphosphate handling and CD73 could improve pathogenic fibroblast dysfunction and tissue regeneration in type 2 inflammatory diseases.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 4","pages":"Pages 1333-1345"},"PeriodicalIF":11.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769159","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":"Mepolizumab in patients with lymphoid-variant hypereosinophilic syndrome: A multicenter prospective study","authors":"Julien Catherine MD ,&nbsp;Sina Karimi MD ,&nbsp;Laurent Dewispelaere MD ,&nbsp;Christophe Lelubre MD, PhD ,&nbsp;Liliane Schandené PhD ,&nbsp;Florence Roufosse MD, PhD","doi":"10.1016/j.jaci.2024.12.1085","DOIUrl":"10.1016/j.jaci.2024.12.1085","url":null,"abstract":"<div><h3>Background</h3><div>Hypereosinophilic syndrome (HES) is characterized by blood and tissue hypereosinophilia causing organ damage and/or dysfunction. Mepolizumab, an anti–IL-5 antibody, has recently been approved in this indication. In lymphoid-variant HES, eosinophil expansion is driven by IL-5–producing clonal CD3⁻CD4⁺ T cells.</div></div><div><h3>Objective</h3><div>This study aimed to elucidate the efficacy of mepolizumab in patients with CD3⁻CD4⁺ lymphoid-variant HES, and the effect of treatment on aberrant cells and associated biomarkers.</div></div><div><h3>Methods</h3><div>A biomarker substudy was conducted during 2 clinical trials evaluating mepolizumab in HES, a 32-week randomized placebo-controlled trial (200622) followed by a 20-week open-label extension (205203). Patients with CD3⁻CD4⁺ and/or clonal T cells, elevated serum TARC/CCL17, soluble (s)CD25, and/or detectable IL-5 were identified, and their treatment responses were compared to those without these anomalies.</div></div><div><h3>Results</h3><div>Of the 108 patients enrolled onto 200622 and 205203, 103 consented to the study, including 17 with a CD3⁻CD4⁺ T-cell subset. Presence of CD3⁻CD4⁺ T cells or serum sCD25 levels ≥1500 pg/mL was associated with reduced eosinophil-lowering and corticosteroid-sparing effects of mepolizumab. None of the biomarkers was associated with an increased likelihood of experiencing clinical flares. A mepolizumab-induced increase in serum IL-5 was observed that was significantly higher in patients with CD3⁻CD4⁺ T cells. Treatment did not affect CD3⁻CD4⁺ T-cell counts.</div></div><div><h3>Conclusion</h3><div>Mepolizumab has a favorable effect on disease flares in patients with CD3⁻CD4⁺ lymphoid-variant HES, although reduced eosinophil-depleting and corticosteroid-sparing effects are observed at the currently approved dose. Further studies are needed to validate these findings on larger patient cohorts, and to explore whether clinical activity other than flares is equally controlled in this disease variant.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 4","pages":"Pages 1299-1309"},"PeriodicalIF":11.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949133","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}

{"title":"Corrigenda","authors":"","doi":"10.1016/j.jaci.2025.02.001","DOIUrl":"10.1016/j.jaci.2025.02.001","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 4","pages":"Page 1400"},"PeriodicalIF":11.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143407975","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}

{"title":"The Editors’ Choice","authors":"","doi":"10.1016/j.jaci.2025.02.016","DOIUrl":"10.1016/j.jaci.2025.02.016","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 4","pages":"Pages 1179-1184"},"PeriodicalIF":11.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143760574","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":"News & Notes-AAAAI","authors":"","doi":"10.1016/S0091-6749(25)00229-5","DOIUrl":"10.1016/S0091-6749(25)00229-5","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 4","pages":"Pages A22-A23"},"PeriodicalIF":11.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143760768","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}