Journal of Allergy and Clinical Immunology最新文献

{"title":"News beyond our pages","authors":"","doi":"10.1016/j.jaci.2025.02.013","DOIUrl":"10.1016/j.jaci.2025.02.013","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 4","pages":"Pages 1185-1186"},"PeriodicalIF":11.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143760575","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":"Uncovering new players in IL-5 signaling: Mast cells, mast cell progenitors, and beyond","authors":"Tanya M. Laidlaw MD","doi":"10.1016/j.jaci.2025.01.037","DOIUrl":"10.1016/j.jaci.2025.01.037","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 4","pages":"Pages 1205-1207"},"PeriodicalIF":11.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382016","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":"COVID-19 mRNA vaccine allergy","authors":"Ágnes Csuth MD , Lene Heise Garvey MD, PhD , Maria C. Jenmalm PhD","doi":"10.1016/j.jaci.2024.10.019","DOIUrl":"10.1016/j.jaci.2024.10.019","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 4","pages":"Pages 1187-1189"},"PeriodicalIF":11.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567306","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":"Mortality in adult patients with chronic spontaneous urticaria: A real-world cohort study","authors":"Pavel Kolkhir MD ,&nbsp;Katja Bieber PhD ,&nbsp;Tomasz Hawro MD ,&nbsp;Khalaf Kridin MD, PhD ,&nbsp;Marlene A. Ludwig ,&nbsp;Henning Olbrich MD ,&nbsp;Martin Metz MD ,&nbsp;Artem Vorobyev MD ,&nbsp;Ralf J. Ludwig MD ,&nbsp;Marcus Maurer MD","doi":"10.1016/j.jaci.2024.11.036","DOIUrl":"10.1016/j.jaci.2024.11.036","url":null,"abstract":"<div><h3>Background</h3><div>Chronic spontaneous urticaria (CSU), a common and debilitating disease, is widely held not to be life limiting, but the mortality of CSU has not been investigated.</div></div><div><h3>Objective</h3><div>We sought to assess all-cause mortality in patients with CSU, risk for comorbidities that are leading causes of death, and impact of guideline-recommended urticaria treatments on mortality rates.</div></div><div><h3>Methods</h3><div>This was a retrospective population-based cohort study of electronic health records of 272,190 adult patients with CSU and 12,728,913 controls without urticaria from the US collaborative network TriNetX.</div></div><div><h3>Results</h3><div>The study included 264,680 propensity score–matched patients with CSU (mean [SD] age = 47.5 [19.8] years; 71.5% female) and a corresponding number of controls without urticaria. Patients with CSU had higher 3-month (hazard ratio [HR] 2.10, 95% CI 1.97-2.22), 1-year (HR 1.77, 95% CI 1.71-1.83), and 5-year (HR 1.69, 95% CI 1.65-1.73) all-cause mortality (all <em>P</em> &lt; .0001). Compared with controls, patients with CSU exhibited higher risk and rates of the leading causes of death in the United States, including suicidal ideations/suicide attempts (HR 3.14, 95% CI 3.00-3.28) and malignant neoplasms (HR 2.09, 95% CI 2.02-2.16). The risk of mortality appeared to be more pronounced in White and younger patients with CSU. All-cause mortality rates at 5 years were significantly lower in patients treated with second-generation H₁ antihistamines versus untreated patients (1.0% vs 2.3%; HR 1.84, <em>P</em> &lt; .0001) and omalizumab-treated patients versus antihistamine-treated patients (0.7% vs 2.6%; HR 3.99, <em>P</em> = .0003).</div></div><div><h3>Conclusions</h3><div>CSU is associated with increased mortality likely due to comorbidities, especially suicide, and effective CSU treatment may reduce mortality. These findings should be investigated in additional studies and in other populations.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 4","pages":"Pages 1290-1298"},"PeriodicalIF":11.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828364","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":"Esophageal epithelial Ikkβ deletion promotes eosinophilic esophagitis in experimental allergy mouse model","authors":"Margarette H. Clevenger PhD ,&nbsp;Cenfu Wei MS ,&nbsp;Adam L. Karami MS ,&nbsp;Lia E. Tsikretsis MS ,&nbsp;Dustin A. Carlson MD ,&nbsp;John E. Pandolfino MD ,&nbsp;Nirmala Gonsalves MD ,&nbsp;Deborah R. Winter PhD ,&nbsp;Kelly A. Whelan PhD ,&nbsp;Marie-Pier Tétreault PhD","doi":"10.1016/j.jaci.2024.12.1070","DOIUrl":"10.1016/j.jaci.2024.12.1070","url":null,"abstract":"<div><h3>Background</h3><div>Eosinophilic esophagitis (EoE) is a chronic T_H2-associated inflammatory disorder triggered by food allergens, resulting in esophageal dysfunction through edema, fibrosis, and tissue remodeling. The role of epithelial remodeling in EoE pathogenesis is critical but not fully understood.</div></div><div><h3>Objective</h3><div>We investigated the role of epithelial IKKβ/NF-κB signaling in EoE pathogenesis using a mouse model with conditional <em>Ikkβ</em> knockout in esophageal epithelial cells (<em>Ikkβ</em>^{<em>EEC-KO</em>}).</div></div><div><h3>Methods</h3><div>EoE was induced in <em>Ikkβ</em>^{<em>EEC-KO</em>} mice through skin sensitization with MC903/ovalbumin followed by intraesophageal ovalbumin challenge. Histologic and transcriptional analyses were performed to assess EoE features. Single-cell RNA sequencing was used to profile esophageal mucosal cell populations and gene expression changes.</div></div><div><h3>Results</h3><div><em>Ikkβ</em>^{<em>EEC-KO</em>}/EoE mice exhibited hallmark EoE features, including eosinophil infiltration, intraepithelial eosinophils, microabscesses, basal cell hyperplasia, and lamina propria remodeling. RNA sequencing revealed significant alterations in IKKβ/NF-κB signaling pathways, with decreased expression of <em>RELA</em> and increased expression of IKKβ-negative regulators. Sequencing analyses identified disrupted epithelial differentiation and barrier integrity alongside increased type 2 immune responses and peptidase activity.</div></div><div><h3>Conclusion</h3><div>Loss of epithelial IKKβ signaling exacerbates EoE pathogenesis, highlighting the critical role of this pathway in maintaining epithelial homeostasis and preventing allergic inflammation. The <em>Ikkβ</em>^{<em>EEC-KO</em>}/EoE mouse model closely mirrors human EoE, providing a valuable tool for investigating disease mechanisms and therapeutic targets. This model can facilitate the development of strategies to prevent chronic inflammation and tissue remodeling in EoE.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 4","pages":"Pages 1276-1289"},"PeriodicalIF":11.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142894580","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":"Respiratory morbidity before and during the COVID-19 pandemic from birth to 18 months in a Swedish birth cohort","authors":"Fanny Kelderer MD ,&nbsp;Gabriel Granåsen PhD ,&nbsp;Sophia Holmlund RNM, PhD ,&nbsp;Sven Arne Silfverdal MD, PhD ,&nbsp;Hilde Bamberg MSc ,&nbsp;Monique Mommers PhD ,&nbsp;John Penders PhD ,&nbsp;Magnus Domellöf MD, PhD ,&nbsp;Ingrid Mogren MD, PhD ,&nbsp;Christina E. West MD, PhD","doi":"10.1016/j.jaci.2024.12.1080","DOIUrl":"10.1016/j.jaci.2024.12.1080","url":null,"abstract":"<div><h3>Background</h3><div>Respiratory infections in early life are an identified risk factor for asthma. We hypothesized that infection-prevention measures during the coronavirus disease 2019 (COVID-19) pandemic influenced the risk of respiratory morbidity and aeroallergen sensitization in early childhood.</div></div><div><h3>Objective</h3><div>We compared respiratory morbidity and aeroallergen sensitization in children born before and during the pandemic.</div></div><div><h3>Methods</h3><div>We compared a COVID-19 category (exposed children; n = 1661) to a pre–COVID-19 category (nonexposed children; n = 1676) by using data from the prospective population-based NorthPop Birth Cohort study in Sweden. Data on respiratory morbidity and concomitant medication were retrieved from national registers. Prospectively collected data on respiratory morbidity using web-based questionnaires at 9 and 18 months of age were applied. At age 18 months, serum IgE levels to aeroallergens were determined (n = 1702).</div></div><div><h3>Results</h3><div>The risk of developing any respiratory tract infection (adjusted odds ratio [aOR] = 0.33 [95% CI, 0.26-0.42]), bronchitis (aOR = 0.50 [95% CI, 0.27-0.95]) and croup (aOR = 0.59 [95% CI, 0.37-0.94]) were decreased in the COVID-19 category. The risk of wheeze in the first 9 months was lower in the COVID-19 category (aOR = 0.70 [95% CI, 0.55-0.89]). There were also fewer prescriptions of antibiotics in the COVID-19 category. The prevalence of aeroallergen sensitization was similar between categories.</div></div><div><h3>Conclusion</h3><div>Children born during the COVID-19 pandemic demonstrated significantly decreased risks of respiratory infections and prescribed antibiotics until 18 months of age compared to children born before the COVID-19 pandemic. Whether this will affect the risk of developing asthma in childhood is being followed.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 4","pages":"Pages 1214-1223.e10"},"PeriodicalIF":11.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903208","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":"A genome-wide meta-analysis reveals shared and population-specific variants for allergic sensitization","authors":"Emiko Noguchi MD, PhD ,&nbsp;Wataru Morii PhD ,&nbsp;Haruna Kitazawa MD, PhD ,&nbsp;Tomomitsu Hirota DDS, PhD ,&nbsp;Kyuto Sonehara MD, PhD ,&nbsp;Hironori Masuko MD, PhD ,&nbsp;Yukinori Okada MD, PhD ,&nbsp;Nobuyuki Hizawa MD, PhD","doi":"10.1016/j.jaci.2024.11.033","DOIUrl":"10.1016/j.jaci.2024.11.033","url":null,"abstract":"<div><h3>Background</h3><div>Allergic diseases are major causes of morbidity in both developed and developing countries and represent a global burden on health care systems. Allergic sensitization is defined as the production of IgE specific to common environmental allergens and is an important indicator in the assessment of allergic diseases.</div></div><div><h3>Objective</h3><div>We sought to clarify the genetic basis of allergic sensitization.</div></div><div><h3>Methods</h3><div>We performed a genome-wide association study (GWAS) of allergic sensitization in the Japanese population followed by a cross-ancestry meta-analysis with a European population including 20,492 cases and 23,342 controls for Japanese and 8,246 cases and 16,786 controls for Europeans. We also performed a polysensitization GWAS of a Japanese population including 4,923 cases and 17,009 controls.</div></div><div><h3>Results</h3><div>Allergic sensitization GWAS identified 18 susceptibility loci for Japanese only and 23 loci for the cross-ancestry population, among which 4 loci were novel. Polysensitization GWAS identified 8 significant loci. Expression quantitative trait locus colocalization analysis revealed polysensitization GWAS significant variants affecting both the phenotype and the expression of the <em>CD28</em>, <em>LPP</em>, and <em>LRCC32</em> genes. Cross-population genetic correlation analysis of allergic sensitization suggested that heterogeneity exists in allergic sensitization between Europeans and Japanese, indicating that more genetic heterogeneity may exist in allergic sensitization than allergic diseases.</div></div><div><h3>Conclusions</h3><div>Our investigation provides new insights into the molecular mechanism of allergic sensitization that could enhance current understanding of allergy and allergic diseases.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 4","pages":"Pages 1321-1332"},"PeriodicalIF":11.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791379","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":"Mesenchymal stem cell-derived small extracellular vesicles restored nasal barrier function in allergic rhinitis via miR-143–GSK3B in human nasal epithelial cells","authors":"Meiqian Xu PhD ,&nbsp;Mei Ren MD ,&nbsp;Xinyin Zhang BA ,&nbsp;Wenxu Peng BA ,&nbsp;Hao Li PhD ,&nbsp;Wenjing Liao PhD ,&nbsp;Jianlei Xie PhD ,&nbsp;Xiaowen Zhang PhD","doi":"10.1016/j.jaci.2024.10.034","DOIUrl":"10.1016/j.jaci.2024.10.034","url":null,"abstract":"<div><h3>Background</h3><div>The nasal epithelial barrier is the first line of defense against the deep entry of pathogens or aeroallergens and is more critical in allergic rhinitis (AR). Restoring epithelial barrier dysfunction might be a promising strategy for AR. Recent studies reported that mesenchymal stem cell–derived small extracellular vesicles (MSC-sEV) potentially inhibit the inflammation response and promote tissue regeneration. However, their effect on nasal epithelial cells remains unknown.</div></div><div><h3>Objectives</h3><div>This study sought to describe the therapeutic effect of MSC-sEV on AR, particularly focusing their effect on nasal epithelial cells and underlying molecular mechanisms.</div></div><div><h3>Methods</h3><div>We utilized an ovalbumin-induced mouse model to study AR. Both primary and immortalized human nasal epithelial cells (HNEpC) were used to further validate the therapeutic effects of MSC-sEV on epithelial cell function. Then we constructed microRNA (miR)-143 overexpressing and low-expressing HNEpC and MSC-sEV to elucidate molecular mechanisms. Transcriptome analysis was performed to identify the downstream pathways involved.</div></div><div><h3>Results</h3><div>MSC-sEV successfully maintained nasal barrier integrity in AR mouse model. The MSC-sEV therapeutic effect on the nasal barrier was substantiated in HNEpC. Mechanistically, miR-143 was a candidate mediator of the above effects. Subsequently, transfecting HNEpC with miR-143 partially mimicked the restoring effect of MSC-sEV. MSC-sEV overexpressing miR-143 exerted more therapeutic effects on tight junctions and barrier integrity. Moreover, miR-143 regulated the glycogen synthase kinase-3β (GSK3B) pathway.</div></div><div><h3>Conclusions</h3><div>Our results indicated that MSC-sEV mitigated AR and restored nasal epithelial barrier dysfunction through the miR-143–GSK3B axis, which suggested that MSC-sEV have the remarkable ability to treat AR.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 4","pages":"Pages 1236-1249.e5"},"PeriodicalIF":11.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620982","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":"DOCK8 at the crossroads of immunodeficiency and hyperinflammation","authors":"Casey A. Rimland MD, PhD ,&nbsp;Michael T. Lam MD, PhD ,&nbsp;Pui Y. Lee MD, PhD","doi":"10.1016/j.jaci.2024.12.1072","DOIUrl":"10.1016/j.jaci.2024.12.1072","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 4","pages":"Pages 1199-1201"},"PeriodicalIF":11.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882109","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 relationship between the early-life gastrointestinal microbiome and childhood nocturnal cough","authors":"Amy A. Eapen MD, MS ,&nbsp;Tengfei Ma PhD ,&nbsp;Alexandra R. Sitarik MS ,&nbsp;Ze Meng MS ,&nbsp;Dennis R. Ownby MD ,&nbsp;Andrea E. Cassidy-Bushrow PhD ,&nbsp;Ganesa Wegeinka PhD ,&nbsp;Edward M. Zoratti MD ,&nbsp;Susan V. Lynch PhD ,&nbsp;Christine C. Johnson PhD ,&nbsp;Albert M. Levin PhD","doi":"10.1016/j.jaci.2025.01.006","DOIUrl":"10.1016/j.jaci.2025.01.006","url":null,"abstract":"<div><h3>Background</h3><div>Nocturnal cough affects approximately 1 in 3 children, can negatively affect child health, and is often attributable to asthma. The association of the gut microbiome with nocturnal cough has not been investigated.</div></div><div><h3>Objective</h3><div>We investigated the association between early-life gut microbiome composition and nocturnal cough overall and in the context of asthma.</div></div><div><h3>Methods</h3><div>Gut microbiota 1-month (neonate) and 6-month (infant) specimens from 512 children in the Wayne County, Health, Environment, Allergy, and Asthma Longitudinal Study were profiled using 16S ribosomal RNA V4 sequencing. Nocturnal cough (parental report) and asthma (parent-reported doctor’s diagnosis) were assessed at age 4 years. Microbiome regression-based kernel association tests (MiRKAT) were used to assess the relationship between gut microbiota composition and nocturnal cough overall and in the context of asthma. Operational taxonomic unit (OTU) associations were conducted using negative binomial regression, adjusting for multiple comparisons using the false discovery rate.</div></div><div><h3>Results</h3><div>Stool microbial composition differences during infancy were associated with nocturnal cough (weighted UniFrac <em>P</em> = .045); 78 OTUs were significantly associated with nocturnal cough overall (false discovery rate &lt; 0.05); and 110 OTUs were significantly associated with nocturnal cough and differed by asthma status (interaction false discovery rate &lt; 0.05), with a predominance of Lachnospiraceae genera <em>Blautia</em> and <em>Dorea.</em> Thirty-two OTU were identified as having both overall effects and differences by asthma status. Among OTUs with significant nocturnal cough-by-asthma interactions, 84 retained significance in children with asthma, with 45 exclusive to those with asthma (predominance of Bacteroidaceae genus <em>Bacteroides</em> and Lachnospiraceae genus <em>Dorea</em>).</div></div><div><h3>Conclusion</h3><div>Infantile gut microbiome development is associated with nocturnal cough and differed by asthma status by age 4 years. Further studies are needed to determine if the gut microbiome may provide additional information for the early identification of children at risk for nocturnal cough, with and without asthma.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 4","pages":"Pages 1386-1391"},"PeriodicalIF":11.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142989381","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}