Journal of Allergy and Clinical Immunology最新文献

{"title":"Respiratory morbidity before and during the COVID-19 pandemic from birth to 18 months in a Swedish birth cohort.","authors":"Fanny Kelderer, Gabriel Granåsen, Sophia Holmlund, Sven Arne Silfverdal, Hilde Bamberg, Monique Mommers, John Penders, Magnus Domellöf, Ingrid Mogren, Christina E West","doi":"10.1016/j.jaci.2024.12.1080","DOIUrl":"10.1016/j.jaci.2024.12.1080","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>We compared respiratory morbidity and aeroallergen sensitization in children born before and during the pandemic.</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-12-27","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thymic and T-cell intrinsic critical roles associated with Severe Combined Immunodeficiency and Omenn syndrome due to a heterozygous variant (G201R) in PSMB10.","authors":"Hye Sun Kuehn, Marita Bosticardo, Antonio C Arrieta, Jennifer L Stoddard, Francesca Pala, Julie E Niemela, Agustin A Gil Silva, Paighton L King, Ana Esteve-Sole, Amreen Naveen, Eduardo Anaya, Pooi Meng Truong, Ottavia M Delmonte, David K Buchbinder, Sergio D Rosenzweig, Luigi D Notarangelo","doi":"10.1016/j.jaci.2024.12.1082","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.12.1082","url":null,"abstract":"<p><strong>Background: </strong>Heterozygous immunoproteasome subunit beta-type 10 (PSMB10) mutations can cause severe combined immunodeficiency (SCID) and Omenn syndrome (OS). Hematopoietic stem cell transplantation in these patients is associated with severe complications and poor immune reconstitution, often resulting in death.</p><p><strong>Objective: </strong>To perform immunological and molecular characterization of an infant with a PSMB10 heterozygous variant.</p><p><strong>Methods: </strong>A heterozygous variant in PSMB10 (p.G201R) was identified in the index but not her parents. Detailed immunophenotyping and functional studies, including flow cytometry, immunoblotting, and T-cell development in artificial thymic organoids (ATO), were performed.</p><p><strong>Results: </strong>The patient presented with severe B-, NK-, as well as T-cell lymphopenia, with a progressive increase in memory CD4+ and loss of CD8+ T-cells, diminished Vbeta family diversity, and abnormal IL-7 signaling. Immunoproteasome protein expression (PSMB10 and 9) was markedly reduced in the patient's cells, including PBMCs, EBV-transformed B cells, and fibroblasts, the mutation likely acting in a dominant negative fashion. Patient CD34+ cells showed a normal early T-cell development but slightly impaired generation of CD3+TCRαβ+ cells in ATO, and human thymus single cell RNA sequencing demonstrated that PSMB10 is expressed in different subsets of cortical and medullary thymic epithelial cells. Collectively, these data indicate that PSMB10 mutations affect positive selection of CD8 T-cells, generation of a diverse T-cell repertoire, and negative selection of autoreactive T-cells.</p><p><strong>Conclusion: </strong>The PSMB10 G201R variant is associated with reduced immunoproteasome expression levels that appear to play vital roles in hematopoietic and extra-hematopoietic immune system development and function. PSMB10-associated thymoproteasome dysfunction leads to impaired thymopoiesis and the development of SCID and OS, suggesting possible benefit from thymus implantation.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903211","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":"Chronic spontaneous urticaria remission definition and therapy stepping down: World Allergy Organization position paper.","authors":"Jorge Sánchez, Helena Pite, René Maximiliano Gómez, Ignacio J Ansotegui, G Walter Canonica, Ignacio Dávila, Marta Ferrer, Jose Luis García Abujeta, Bryan Martin, Mário Morais-Almeida, José António Ortega Martell, María Isabel Rojo Gutierrez, Jonathan A Bernstein","doi":"10.1016/j.jaci.2024.11.039","DOIUrl":"10.1016/j.jaci.2024.11.039","url":null,"abstract":"<p><strong>Background: </strong>There is no global agreement on the definition of chronic spontaneous urticaria (CSU) remission.</p><p><strong>Objective: </strong>Our aim was to generate a consensus for clinical definitions of CSU-related terms focused on remission.</p><p><strong>Methods: </strong>The World Allergy Organization Urticaria Committee systematically reviewed current available longitudinal articles. On the basis of this review, a consensus agreement was reached for the definition of the term CSU remission. In addition, a scheme specifying when and how therapeutic de-escalation should be performed was constructed.</p><p><strong>Results: </strong>Almost all of the groups that have carried out longitudinal studies to evaluate the frequency of CSU remission agreed to use the term CSU remission if the patient remains without urticaria signs and symptoms without pharmacologic treatment (omalizumab, cyclosporine, antihistamines, or systemic corticosteroids). According to our systematic review, the available evidence does not specify the best time to consider CSU remission. However, current evidence suggests that there is no significant difference in CSU relapse between 6- and 12-month periods of remission. So far, no evidence exists to propose any biomarkers for defining inflammatory or mechanistic remission in CSU or identifying patients with a high probability of cure. It can be reasonable to consider a reduction of treatment after 6 months of CSU control, with evaluation 2 to 6 months after stepping down treatment.</p><p><strong>Conclusion: </strong>The World Allergy Organization Urticaria Committee proposes defining CSU clinical remission based on the total resolution of urticaria signs and symptoms without pharmacotherapy for at least 6 months. The implications of this definition in clinical practice must be evaluated and validated in future studies.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142894567","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":"Somatic mosaicism in genetic errors of immunity.","authors":"Megan A Cooper","doi":"10.1016/j.jaci.2024.11.038","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.11.038","url":null,"abstract":"Genetic mosaicism in somatic cells can lead to the presence of pathogenic variants in a subset of immune cells causing genetic errors of immunity (GEI), often phenocopying germline inborn errors of immunity (IEI). Over the last two decades significant progress has been made in the identification of these disorders in patients, including discovery of new diseases. Diagnosis of disease-causing somatic mosaicism provides a target for treatment and monitoring of patients and has implications for genetic counseling. However, there continue to be barriers in the identification of somatic mosaicism, particularly for the clinical diagnosis of patients, based on the limitations of current diagnostic sequencing and analysis approaches. This review focuses on how somatic mosaicism can lead to GEI, the genes known to be associated with somatic GEI, and challenges in the field for accurate diagnosis of patients.","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"5 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887520","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 Monogenic Landscape of Human Infectious Diseases.","authors":"Stéphanie Boisson-Dupuis,Paul Bastard,Vivien Béziat,Jacinta Bustamante,Aurélie Cobat,Emmanuelle Jouanguy,Anne Puel,Jérémie Rosain,Qian Zhang,Shen-Ying Zhang,Bertrand Boisson","doi":"10.1016/j.jaci.2024.12.1078","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.12.1078","url":null,"abstract":"The spectrum of known monogenic inborn errors of immunity is growing, with certain disorder underlying a specific and narrow range of infectious diseases. These disorders reveal the core mechanisms by which these infections occur in various settings, including inherited and acquired immunodeficiencies, thereby delineating the essential mechanisms of protective immunity to the corresponding pathogens. These findings also have medical implications, facilitating diagnosis and improving the management of individuals at risk of disease.","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"87 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887524","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":"Interplay between on-demand treatment trials for hereditary angioedema and treatment guidelines.","authors":"Danny M Cohn,Daniel F Soteres,Timothy J Craig,William R Lumry,Markus Magerl,Marc A Riedl,Paul K Audhya,Marcus Maurer,Jonathan A Bernstein","doi":"10.1016/j.jaci.2024.12.1079","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.12.1079","url":null,"abstract":"Over the past two decades, guidelines for the on-demand treatment of hereditary angioedema (HAE) attacks have undergone significant evolution. Early treatment guidelines, such as the Canadian 2003 International Consensus Algorithm, often gated on-demand treatment by attack location and/or severity. Pivotal trials for on-demand injectable treatments (plasma-derived C1 esterase inhibitor [C1INH], icatibant, ecallantide [US only], recombinant C1INH), which were approved in the US and EU between 2008-2014, were designed accordingly. Subsequent post hoc analyses of clinical trial data alongside real-world evidence led to a paradigm shift. In 2013, the US HAE Association guidelines recommended that all attacks, irrespective of location or severity, be considered for treatment as early as possible after onset to minimize morbidity and mortality. This approach remains the cornerstone of current treatment guidelines and has shaped the design of recent clinical trials, such as those for the investigational agents, oral plasma kallikrein inhibitor sebetralstat and oral bradykinin B2 receptor antagonist deucrictibant. This narrative review discusses the evolution of on-demand treatment guidelines, the clinical trial and real-world data that prompted significant revisions, and the subsequent changes to trial designs introduced to facilitate guideline compliance.","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"42 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887525","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":"Esophageal epithelial Ikkβ deletion promotes eosinophilic esophagitis in experimental allergy mouse model.","authors":"Margarette H Clevenger, Cenfu Wei, Adam L Karami, Lia E Tsikretsis, Dustin A Carlson, John E Pandolfino, Nirmala Gonsalves, Deborah R Winter, Kelly A Whelan, Marie-Pier Tétreault","doi":"10.1016/j.jaci.2024.12.1070","DOIUrl":"10.1016/j.jaci.2024.12.1070","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>We investigated the role of epithelial IKKβ/NF-κB signaling in EoE pathogenesis using a mouse model with conditional Ikkβ knockout in esophageal epithelial cells (Ikkβ^EEC-KO).</p><p><strong>Methods: </strong>EoE was induced in Ikkβ^EEC-KO 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.</p><p><strong>Results: </strong>Ikkβ^EEC-KO/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 RELA 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.</p><p><strong>Conclusion: </strong>Loss of epithelial IKKβ signaling exacerbates EoE pathogenesis, highlighting the critical role of this pathway in maintaining epithelial homeostasis and preventing allergic inflammation. The Ikkβ^EEC-KO/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.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-12-24","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":"Update on inborn errors of immunity.","authors":"Hanna IJspeert,Emily S J Edwards,Robyn E O'Hehir,Virgil A S H Dalm,Menno C van Zelm","doi":"10.1016/j.jaci.2024.12.1075","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.12.1075","url":null,"abstract":"Ever since the first description of an inherited immunodeficiency in 1952 in a boy with gammaglobulin deficiency, new insights have progressed rapidly in disorders that are now referred to as inborn errors of immunity (IEI). In a field where fundamental molecular biology, genetics, immune signaling and clinical care are tightly intertwined, 2022-2024 saw a multitude of advances. Here we report a selection of research updates with a main focus on (1) diagnosis and screening, (2) new genetic defects, (3) susceptibility to severe COVID-19 infection and impact of vaccination, and (4) treatment. Importantly, new pathogenic insights more rapidly impact on treatment outcomes, either through an earlier and more precise diagnosis, or through implementation of novel, personalized treatment. As the field is growing rapidly, awareness, communication and collaboration are key to improving treatment outcomes.","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"308 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887634","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":"Early-life microRNA signatures in cord blood associated with allergic rhinitis and asthma development.","authors":"Hooman Mirzakhani,Alberta L Wang,Rinku Sharma,Maoyun Sun,Ronald Panganiban,Quan Lu,Michael McGeachie,Zheng Lu,Augusto A Litonjua,Kelan G Tantisira,Scott T Weiss","doi":"10.1016/j.jaci.2024.12.1077","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.12.1077","url":null,"abstract":"BACKGROUNDMicroRNAs (miRNAs) are involved in the biological regulation of asthma and allergies.OBJECTIVESTo investigate the association between cord blood miRNAs and the development of allergic rhinitis and early childhood asthma.METHODSmiRNAs were sequenced from cord blood of subjects participating in the Vitamin D Antenatal Asthma Reduction Trial. Multivariable miRNA differential expression analyses were performed to examine their association with physician diagnosed asthma and allergic rhinitis by age 3, as well as active asthma status at age 6 years. miRNA signatures were further investigated for their ability to induce human airway smooth muscle cell (HASMC) proliferation in vitro.RESULTSIn a cohort of 389 subjects, elevated cord blood expression of miR-149-5p was associated with both age 3 allergic rhinitis and asthma (log2FC: 1.87 and 1.42, respectively, FDR<0.001), as well as age 6 active asthma status (log2FC: 2.26, FDR<0.001). Higher expressions of miR-99b-5p, miR-125a-5p, and miR-200c-3p were also associated with both diagnosis of allergic rhinitis at age of 3 years and active asthma status at age of 6 (allergic rhinitis: log2FC: 0.6, 0.62, and 1.06, respectively, FDR<0.001; active asthma: log2FC: 0.55, 0.60, 1.10, respectively, FDR<0.001, respectively). Higher expression of miR-145-5p was associated with both new onset asthma after age 3 and active asthma status at age 6 (log2FC: 0.73 and 0.40, FDR<0.001, respectively). These five miRNA signatures target key hubs in the interactome module of 71 genes associated with allergic rhinitis and asthma. Transfection of miR-125a-5p and miR-145-5p into HASMC induced cell proliferation.CONCLUSIONThe dysregulation of cord blood miRNAs at birth are associated with allergic rhinitis and early childhood asthma. The miRNAs that regulate post-embryonic development and immune response may serve as potential biomarkers and preventive targets for asthma.","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"25 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887522","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":"NLRC4-associated autoinflammatory disease: insights from mouse models and somatic variants.","authors":"Mathijs Willemsen,Willem Roosens,Frederik Staels,Thea H M Schoonbrood,Rik Schrijvers","doi":"10.1016/j.jaci.2024.12.1076","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.12.1076","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"64 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887523","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}