Journal of Allergy and Clinical Immunology最新文献

{"title":"Novel insights on the biology and immunologic effects of histamine: A road map for allergists and mast cell biologists","authors":"Sima Heidarzadeh-Asl MSc ,&nbsp;Marcus Maurer MD ,&nbsp;Amir Kiani PhD ,&nbsp;Dmitrii Atiakshin PhD ,&nbsp;Per Stahl Skov MD, PhD ,&nbsp;Daniel Elieh-Ali-Komi MSc","doi":"10.1016/j.jaci.2024.12.1081","DOIUrl":"10.1016/j.jaci.2024.12.1081","url":null,"abstract":"<div><div>Histamine (C₅H₉N₃, molecular weight 111.15 g/mol) is a well-studied endogenous biogenic amine composed of an imidazole ring attached to an ethylamine side chain. It has a limited half-life of a few minutes within tissues and in circulation. Several cell types including mast cells (MCs), basophils, platelets, histaminergic neurons, and enterochromaffin cells produce varying amounts of histamine using histidine decarboxylase. However, only MCs and basophils have complex mechanisms to pack and store histamine in granules along with other mediators using serglycin and its carried glycosaminoglycan side chains. Relatively low granule pH (∼5.5) supports the binding of stored histamine to heparin, whereas exposure to neutral pH after degranulation weakens the binding and histamine becomes liberated. Histamine exerts multifaceted regulatory biofunctions by engaging its 4 types of heptahelical G protein–coupled receptors (H1R-H4R), which have different expression profiles and functions. MCs express H1R, H2R, and H4R, which gives them a dual role in histamine biology as producers and responsive target cells. Histamine plays a role in a variety of physiologic and pathologic processes such as cell proliferation, differentiation, hematopoiesis, vascular permeability, embryogenesis, tissue regeneration, and wound healing. The emergence of histamine receptor–deficient mouse models and the development of multiple histamine receptor agonists and antagonists have helped researchers better understand these physiologic and pathogenic functions of histamine. We review the biology of histamine with a focus on immunologic aspects and the role of histamine in allergy and MC biology.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 4","pages":"Pages 1095-1114"},"PeriodicalIF":11.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903206","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":"Respiratory mucosal plasma exudation in human innate and adaptive immunity","authors":"Carl Persson PhD","doi":"10.1016/j.jaci.2025.01.011","DOIUrl":"10.1016/j.jaci.2025.01.011","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 4","pages":"Pages 1190-1195"},"PeriodicalIF":11.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991744","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":"Eosinophils promote the production of autoantibodies in bullous pemphigoid","authors":"Hideyuki Ujiie MD, PhD","doi":"10.1016/j.jaci.2025.01.027","DOIUrl":"10.1016/j.jaci.2025.01.027","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 4","pages":"Pages 1208-1210"},"PeriodicalIF":11.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122844","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":"Update on atopic dermatitis","authors":"Shannon Meledathu BS,&nbsp;Malini P. Naidu BA,&nbsp;Patrick M. Brunner MD, MSc","doi":"10.1016/j.jaci.2025.01.013","DOIUrl":"10.1016/j.jaci.2025.01.013","url":null,"abstract":"<div><div>Atopic dermatitis is the most common chronic inflammatory skin condition. This review highlights most recent advances in understanding and treating this debilitating disease. We summarize new insights regarding molecular endotypes and clinical phenotypes that characterize atopic dermatitis, the role of the skin microbiome, and improvements in diagnostic tools. We also emphasize recent scientific advancements in understanding the mechanisms driving atopic dermatitis pathogenesis and discuss the identification and implementation of new targeted treatment approaches that have revolutionized therapeutic options for affected patients.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 4","pages":"Pages 1124-1132"},"PeriodicalIF":11.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038988","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":"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":"COVID-19 mRNA vaccine allergy","authors":"Ágnes Csuth MD ,&nbsp;Lene Heise Garvey MD, PhD ,&nbsp;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}