Journal of Allergy and Clinical Immunology最新文献

{"title":"Opportunities for using artificial intelligence in air pollution and health research.","authors":"Roger D Peng, Sarah E Chambliss","doi":"10.1016/j.jaci.2024.09.022","DOIUrl":"10.1016/j.jaci.2024.09.022","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142377929","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":"Clinical effectiveness and safety of dupilumab in patients with chronic obstructive pulmonary disease: A 7-year population-based cohort study.","authors":"Chuan-Yen Sun, Yohannes Tesfaigzi, Gin-Yi Lee, Yi-Hsuan Chen, Scott T Weiss, Kevin Sheng-Kai Ma","doi":"10.1016/j.jaci.2024.09.019","DOIUrl":"10.1016/j.jaci.2024.09.019","url":null,"abstract":"<p><strong>Background: </strong>Previous randomized controlled trials have established the efficacy of dupilumab among patients with chronic obstructive pulmonary disease (COPD) treated with triple therapy over 52 weeks of follow-up.</p><p><strong>Objective: </strong>This population-based cohort study aimed to explore the long-term safety and effectiveness of dupilumab in patients with COPD.</p><p><strong>Methods: </strong>The study included US patients with COPD who were seen between April 2017 and August 2024. Patients initiating dupilumab and therapies that incorporated long-acting β₂-agonist (LABA) inhalers were included. Patients with asthma or lung cancer were excluded. The risk of outcomes occurring after initiation of dupilumab versus LABA-containing therapies was measured. For detailed methods, please see the Methods section in this article's Online Repository at www.jacionline.org.</p><p><strong>Results: </strong>A total of 1521 dupilumab initiators and 1521 propensity score-matched patients who were receiving LABA-based therapies were included. Receiving dupilumab was associated with lower all-cause mortality (hazard ratio [HR] = 0.53, 95% CI = 0.43-0.65), fewer emergency department visits (HR = 0.78, 95% CI =0.69-0.89), and lower acute exacerbation rates (HR = 0.59, 95% CI = 0.53-0.65). Dupilumab was also associated with reductions in the requirement for short-acting β₂-agonists (HR = 0.48, 95% CI = 0.43-0.52) and short-acting muscarinic antagonists (HR = 0.43, 95% CI = 0.37-0.49) for symptom control. Additionally, dupilumab decreased rates of subsequent pneumonia (HR = 0.65, 95% CI = 0.50-0.86), and COPD-relevant comorbidities, including new-onset heart failure (HR = 0.69, 95% CI = 0.53-0.90) and new-onset anxiety (HR = 0.70, 95% CI =0.53-0.93).</p><p><strong>Conclusions: </strong>In patients with COPD, dupilumab was associated with a lower mortality rate, fewer emergency department visits, and a reduced risk of acute exacerbations, respiratory symptoms, and respiratory infections. More studies are needed to validate the efficacy of dupilumab among patients with COPD of various severities.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142377928","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":"Role of anti-IgE in immediate drug allergy.","authors":"Lily Li, Kimberly G Blumenthal","doi":"10.1016/j.jaci.2024.09.021","DOIUrl":"10.1016/j.jaci.2024.09.021","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375420","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":"Phenotypic and pathomechanistic overlap between tapasin and TAP deficiencies","authors":"","doi":"10.1016/j.jaci.2024.06.003","DOIUrl":"10.1016/j.jaci.2024.06.003","url":null,"abstract":"<div><h3>Background</h3><div>Human tapasin deficiency is reported to cause an autosomal-recessive inborn error of immunity characterized by substantially reduced cell surface expression of major histocompatibility complex class I (MHC-I).</div></div><div><h3>Objective</h3><div>We evaluated the immunologic and clinical consequences of tapasin deficiency.</div></div><div><h3>Methods</h3><div>A novel homozygous variant in <em>TAPBP</em> was identified by means of whole genome sequencing. The expression of tapasin and both subunits of the transporter associated with antigen presentation (TAP) were evaluated by Western blot analysis. Cell surface and intracellular expression of MHC-I were evaluated by flow cytometry. Small interfering RNAs were used for silencing <em>TAPBP</em> expression in HEK293T cells.</div></div><div><h3>Results</h3><div>We identified a deletion in <em>TAPBP</em> (c.312del, p.(K104Nfs∗6)) causing tapasin deficiency in a patient with bronchiectasis and recurrent respiratory tract infections as well as herpes zoster. Besides substantial reduction in TAP1 and TAP2 expression, peripheral blood mononuclear cells from this patient and <em>TAPBP</em>-knockdown HEK293T cells, displayed reduced cell surface expression of MHC-I, while reduction in intracellular expression of MHC-I was less prominent, suggesting a defect in MHC-I trafficking to the plasma membrane. IFN-α improved cell surface expression of MHC-I in tapasin deficient lymphocytes and <em>TAPBP</em>-knockdown HEK293T cells, representing a possible therapeutic approach for tapasin deficiency.</div></div><div><h3>Conclusion</h3><div>Tapasin deficiency is a very rare inborn error of immunity, the pathomechanism and clinical spectrum of which overlaps with TAP deficiencies.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"154 4","pages":"Pages 1069-1075"},"PeriodicalIF":11.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141310786","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":"Nonsense CD247 mutations show dominant-negative features in T-cell receptor expression and function","authors":"","doi":"10.1016/j.jaci.2024.06.019","DOIUrl":"10.1016/j.jaci.2024.06.019","url":null,"abstract":"<div><h3>Background</h3><div>The invariant TCR ζ/CD247 homodimer is crucial for TCR/CD3 expression and signaling through its 3 immunoreceptor tyrosine-based activation motifs (ITAMs). Homozygous null mutations in <em>CD247</em> lead to immunodeficiency, while carriers exhibit 50% reduced surface CD3. It is unclear whether carriers of other <em>CD247</em> variants show dominant-negative effects.</div></div><div><h3>Objective</h3><div>We sought to analyze and model the potential impact on T-cell receptor (TCR) expression and function of heterozygous nonsense <em>CD247</em> mutations found in patients with signs of immunodeficiency or autoimmunity.</div></div><div><h3>Methods</h3><div>Jurkat T cells, either wild-type (WT) or CRISPR/Cas9-edited CD247-deficient (ZKO), were lentivirally transduced with WT CD247 or mutations ablating 1 (Q142X), 2 (Q101X), or 3 (Q70X) ITAMs.</div></div><div><h3>Results</h3><div>Three patients from unrelated families were studied. Two heterozygous nonsense <em>CD247</em> mutations were identified (p.Y152X and p.Q101X), which affected ITAM-3 and ITAM-2 and ITAM-3, respectively. Both mutations were associated with low surface CD3 expression and normal intracellular CD247 levels using a transmembrane-specific antibody, but very low intracellular CD247 levels using an ITAM-3–specific one, suggesting the presence of truncated variants in T cells. Transduction of the mutations lacking 1, 2, or 3 ITAMs into ZKO cells could not restore normal surface CD3 expression (only 60%, 22%, and 10%, respectively), whereas in WT cells, normal surface CD3 expression was reduced (to 39%, 19%, and 9% of normal levels), and both effects were dependent on ITAM number. All 6 transfectants showed reduced CD69 induction (25% to 50%), indicating that they were unable to signal downstream properly, neither isolated nor associated with WT CD247.</div></div><div><h3>Conclusions</h3><div>Our results suggest that <em>CD247</em> variants lacking ITAMs due to nonsense, but not null, mutations are defective for normal TCR assembly and exert a dominant-negative effect on TCR expression and signaling <em>in vitro</em>. This, in turn, may correlate with clinical features <em>in vivo</em>.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"154 4","pages":"Pages 1022-1032"},"PeriodicalIF":11.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590406","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":"Indoor air pollution and airway health","authors":"Jared Radbel MD ,&nbsp;Meghan E. Rebuli PhD ,&nbsp;Howard Kipen MD, MPH ,&nbsp;Emily Brigham MD, MHS","doi":"10.1016/j.jaci.2024.08.013","DOIUrl":"10.1016/j.jaci.2024.08.013","url":null,"abstract":"<div><div>Because of the disproportionate amount of time that people spend indoors and the complexities of air pollutant exposures found there, indoor air pollution is a growing concern for airway health. Both infiltration of outdoor air pollution into the indoor space and indoor sources (such as smoke from tobacco products, cooking or heating practices and combustion of associated fuels, and household materials) contribute to unique exposure mixtures. Although there is substantial literature on the chemistry of indoor air pollution, research focused on health effects is only beginning to emerge and remains an important area of need to protect public health. We provide a review of emerging literature spanning the past 3 years and relating indoor air exposures to airway health, with a specific focus on the impact of either individual pollutant exposures or common combustion sources on the lower airways. Factors defining susceptibility and/or vulnerability are reviewed with consideration for priority populations and modifiable risk factors that may be targeted to advance health equity.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"154 4","pages":"Pages 835-846"},"PeriodicalIF":11.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055625","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":"Obesity and Hormonal Influences on Asthma: Mechanisms, Management Challenges, and Emerging Therapeutic Strategies.","authors":"Natalia Weare-Regales, Tara Carr, Fernando Holguin, Christopher Andrew Tibbitt, Richard F Lockey","doi":"10.1016/j.jaci.2024.09.018","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.09.018","url":null,"abstract":"<p><p>Obesity and hormonal dysregulation, common comorbidities of asthma, not only influence asthma risk and onset but can also complicate its management. The pathobiological characteristics of obesity, such as insulin resistance and metabolism alterations, can impact lung function and airway inflammation while highlighting potential opportunities for therapeutic intervention. Likewise, obesity alters immune cell phenotypes and corticosteroid pharmacokinetics. Hormones such as sex hormones, incretins, and thyroid hormones can also affect asthma. This review highlights the mechanisms underlying obesity-related asthma and hormonal pathologies while exploring potential therapeutic strategies and the need for more research and innovative approaches in managing these comorbid conditions.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371936","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":"Single cell RNA sequencing of human eosinophils from nasal polyps reveals eosinophil heterogeneity in chronic rhinosinusitis tissue","authors":"","doi":"10.1016/j.jaci.2024.05.014","DOIUrl":"10.1016/j.jaci.2024.05.014","url":null,"abstract":"<div><h3>Background</h3><div>Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by type 2 inflammation in the United States, but the actual roles that eosinophils play in CRSwNP remain largely unclear.</div></div><div><h3>Objective</h3><div>To reveal the roles and heterogeneity of eosinophils in nasal polyp (NP) tissue, we performed single cell RNA sequencing (scRNA-Seq) analysis of NP tissue.</div></div><div><h3>Methods</h3><div>Sinonasal tissues (NP and control sinus tissue) and patient matched peripheral blood (PB) samples were obtained from 5 control patients and 5 patients with CRSwNP. Eosinophils were enriched before processing for scRNA-Seq. The gene expression profiles in eosinophils were determined by microwell-based scRNA-Seq technology (BD Rhapsody platform). We predicted the overall function of NP eosinophils by Gene Ontology (<span><span>geneontology.org</span><svg><path></path></svg></span>) enrichment and pathway analyses and confirmed expression of selected genes by flow cytometry.</div></div><div><h3>Results</h3><div>After filtering out contaminating cells, we detected 5,542 eosinophils from control PB, 3,883 eosinophils from CRSwNP PB, 101 eosinophils from control sinus tissues (not included in further analyses), and 9,727 eosinophils from NPs by scRNA-Seq. We found that 204 genes were downregulated and 354 genes upregulated in NP eosinophils compared to all PB eosinophils (&gt;1.5-fold, <em>P</em>_adj &lt; .05). Upregulated genes in NP eosinophils were associated with activation, cytokine-mediated signaling, growth factor activity, NF-κB signaling, and antiapoptotic molecules. NP eosinophils displayed 4 clusters revealing potential heterogeneity of eosinophils in NP tissue.</div></div><div><h3>Conclusions</h3><div>Elevated eosinophils in NP tissue appear to exist in several subtypes that may play important pathogenic roles in CRSwNP, in part by controlling inflammation and hyperproliferation of other cells.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"154 4","pages":"Pages 952-964"},"PeriodicalIF":11.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141135154","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 beyond our pages - October 2024","authors":"","doi":"10.1016/j.jaci.2024.08.007","DOIUrl":"10.1016/j.jaci.2024.08.007","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"154 4","pages":"Pages 909-910"},"PeriodicalIF":11.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142428609","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":"Indoor air: Guidelines, policies, and regulation","authors":"","doi":"10.1016/j.jaci.2024.06.015","DOIUrl":"10.1016/j.jaci.2024.06.015","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"154 4","pages":"Pages 911-913"},"PeriodicalIF":11.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476581","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}