Journal of Allergy and Clinical Immunology最新文献

{"title":"Efficacy and safety of GR1802 in uncontrolled chronic rhinosinusitis with nasal polyps: Placebo-controlled phase 2 trial","authors":"Ming Zheng MD, PhD ,&nbsp;Di Wu MD, PhD ,&nbsp;Yingshi Piao MD ,&nbsp;Jun Tang MD ,&nbsp;Fang Quan MD ,&nbsp;Bing Guan PhD ,&nbsp;Hongmeng Yu PhD ,&nbsp;Xiaowen Zhang MD ,&nbsp;Gang He MD ,&nbsp;Yucheng Yang MD ,&nbsp;Lijia Wan MD ,&nbsp;Xuezhong Li MD ,&nbsp;Wen Liu MD ,&nbsp;Zhendong Xu MD ,&nbsp;Jing Ye MD, PhD ,&nbsp;Wen Liu MD ,&nbsp;Xicheng Song MD ,&nbsp;Yuxiao Du MD ,&nbsp;Yu Xu MD ,&nbsp;Jianjun Chen MD ,&nbsp;Luo Zhang MD, PhD","doi":"10.1016/j.jaci.2025.01.034","DOIUrl":"10.1016/j.jaci.2025.01.034","url":null,"abstract":"<div><h3>Background</h3><div>Anti–IL-4 receptor subunit alpha (IL-4Rα) treatments can effectively treat eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP). However, their impact on the overall population of patients with uncontrolled CRSwNP remains unclear.</div></div><div><h3>Objectives</h3><div>We evaluated the safety and efficacy of GR1802, a novel anti–IL-4Rα monoclonal antibody, in patients with uncontrolled CRSwNP.</div></div><div><h3>Methods</h3><div>Seventy patients with uncontrolled CRSwNP were randomized (1:1) to receive either GR1802 (300 mg with an initial doubled dose) or placebo every 2 weeks. Primary end points were the changes from baseline in nasal polyp score and nasal congestion score at week 16. Secondary end points mainly included change from baseline in Total Nasal Symptom Score (TNSS), 22-item Sino-Nasal Outcome Test (SNOT-22) score, and Lund-Mackay score. Efficacy (exploratory) was also analyzed in ECRSwNP and non-ECRSwNP subgroups. Safety was evaluated throughout the study.</div></div><div><h3>Results</h3><div>In uncontrolled CRSwNP participants, GR1802 significantly improved nasal polyp score and nasal congestion score compared with placebo, with least squares mean differences of −2.1 (95% confidence interval, −2.6, −1.5) and −0.8 (95% confidence interval, −1.1, −0.4), respectively. Participants treated with GR1802 had significantly decreased TNSS, SNOT-22 score, and Lund-Mackay score. The subgroup analysis demonstrated that GR1802 improved the symptoms and quality of life in both ECRSwNP and non-ECRSwNP participants, as evidenced by changes in nasal polyp score, University of Pennsylvania Smell Identification Test score, and Lund-Mackay score. Treatment-related adverse events occurred in 19.4% of the GR1802 group and 17.6% of the placebo group.</div></div><div><h3>Conclusion</h3><div>GR1802 is well tolerated and effective in treating the overall population with uncontrolled CRSwNP.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 5","pages":"Pages 1575-1583"},"PeriodicalIF":11.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382593","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 and mechanistic advancements in aspirin exacerbated respiratory disease","authors":"Shabnam Elahi MD,&nbsp;Anju T. Peters MD, MSCI,&nbsp;Atsushi Kato PhD,&nbsp;Whitney W. Stevens MD, PhD","doi":"10.1016/j.jaci.2025.03.006","DOIUrl":"10.1016/j.jaci.2025.03.006","url":null,"abstract":"<div><div>Aspirin-exacerbated respiratory disease (AERD) is characterized by the clinical triad of chronic rhinosinusitis with nasal polyps, asthma, and a hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs). AERD is estimated to occur in as many as 15% of patients with chronic rhinosinusitis with nasal polyps and/or asthma. Uniquely, patients with AERD develop respiratory symptoms within 30 to 180 minutes after ingesting NSAIDs such as aspirin or ibuprofen. However, even in the absence of NSAIDs, patients tend to have more severe upper and lower respiratory disease. The underlying pathogenic mechanisms contributing to AERD are complex and intertwined; they include a systemic dysregulation in arachidonic acid metabolism, an aberrant inflammatory response, a disruption in the respiratory epithelial barrier, and an imbalance between the formation and degradation of fibrin locally in nasal polyps. This review will highlight novel mechanistic findings contributing to the pathogenesis of AERD. In addition, recent advancements in the clinical understanding and management of patients with AERD will be discussed.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 5","pages":"Pages 1411-1419"},"PeriodicalIF":11.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669922","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","authors":"","doi":"10.1016/j.jaci.2025.03.010","DOIUrl":"10.1016/j.jaci.2025.03.010","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 5","pages":"Pages 1470-1473"},"PeriodicalIF":11.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143903706","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":"Integrative epidemiology and immunotranscriptomics uncover a risk and potential mechanism for cutaneous lymphoma unmasking or progression with dupilumab therapy","authors":"Javier S. Cabrera-Perez MD, PhD ,&nbsp;Vincent J. Carey PhD ,&nbsp;Oreofe O. Odejide MD, MPH ,&nbsp;Sonal Singh MD, MPH ,&nbsp;Thomas S. Kupper MD ,&nbsp;Shiv S. Pillai MBBS, PhD ,&nbsp;Scott T. Weiss MD, MS ,&nbsp;Ayobami Akenroye MBChB, MPH, PhD","doi":"10.1016/j.jaci.2024.10.028","DOIUrl":"10.1016/j.jaci.2024.10.028","url":null,"abstract":"<div><h3>Background</h3><div>There have been multiple reports of the anti–IL-4Rα agent, dupilumab, being associated with the onset and/or progression of cutaneous T-cell lymphoma (CTCL).</div></div><div><h3>Objective</h3><div>We sought to evaluate safety signals associated with dupilumab, with a focus on CTCL, and to evaluate the possible underlying mechanism or mechanisms for the potential association.</div></div><div><h3>Methods</h3><div>First, we used the Food and Drug Administration’s pharmacovigilance database, FAERS (FDA Adverse Event Reporting System), to evaluate whether dupilumab was associated with CTCL, including both positive outcome controls (conjunctivitis, eosinophilia, and arthralgia) and exposure controls (other medications with similar indications, including JAK inhibitors and the anti–IL-13 agent, tralokinumab) to evaluate confounding bias. Thereafter, we used publicly available bulk and single-cell RNA sequencing datasets to probe possible underlying mechanisms through which dupilumab might be associated with CTCL.</div></div><div><h3>Results</h3><div>Between January 2017 and the fourth quarter of 2023, there were 181,575 unique reports of dupilumab-related adverse events (AEs) in FAERS, with 606 of these being for a neoplasm. Dupilumab had 30.0 times the proportional reporting ratio (PRR) (95% confidence interval, 25.0-35.9) for CTCL compared to all other medications in FAERS. The risk was highest in men aged 45 to 65. The PRR for conjunctivitis, eosinophilia, and arthralgia, known adverse effects of dupilumab, were 35.6 (34.4-36.8), 2.15 (2.00-2.31), and 2.14 (2.07-2.18), respectively. Using the log-count normalized PRR (AE score) to account for PRR inflation when reports were small, the top safety signals included conjunctivitis (AE score 8.3) and CTCL (AE score 4.9). Bulk RNA sequencing data showed changes in IL-4RA and IL-13RA1 expression in CTCL and in epidermal layers of atopic dermatitis (AD) biopsy samples. Single-cell transcriptomic studies revealed that this change was similar in AD and CTCL, and that keratinocytes seemed to be the most divergent cell type with regards to IL-4R and IL-13RA1. An effect on keratinocyte-specific gene expression was also independently observed in available bulk RNA sequencing data.</div></div><div><h3>Conclusion</h3><div>These data suggest that dupilumab might be causing an unmasking or progression of CTCL via the same mechanism through which it improves AD: IL-13 receptor blockade, which leads to increased IL-13 in the local milieu, driving CTCL stimulation and progression. However, these associations need further evaluation given the inherent limitations of the FAERS database and our nonexperimental approach.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 5","pages":"Pages 1584-1594"},"PeriodicalIF":11.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620978","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":"Deficiency of adenosine deaminase 2 skews adaptive immune repertoires toward specific sets of T- and B-cell receptors","authors":"Christoph Schultheiß PhD ,&nbsp;Paul Schmidt-Barbo MSc ,&nbsp;Lisa Paschold PhD ,&nbsp;Carl Esperanzate BSc ,&nbsp;Alissa Behn MSc ,&nbsp;Rafael Mikolajczyk MD, MSc ,&nbsp;Daniel L. Kastner MD, PhD ,&nbsp;Ivona Aksentijevich MD ,&nbsp;Mascha Binder MD","doi":"10.1016/j.jaci.2025.01.032","DOIUrl":"10.1016/j.jaci.2025.01.032","url":null,"abstract":"<div><h3>Background</h3><div>Adenosine deaminase 2 deficiency (DADA2) is a genetic disorder caused by biallelic hypomorphic or loss-of-function mutations in the <em>ADA2</em> gene, which encodes a protein deaminase regulating extracellular adenosine metabolism. Clinical features encompass inflammatory vasculopathy, early-onset strokes, and a complex presentation involving both immunodeficiency and autoinflammation/autoimmunity.</div></div><div><h3>Objective</h3><div>Our aim was to determine a DADA2-specific adaptive immune architecture.</div></div><div><h3>Methods</h3><div>We profiled immunoglobulin levels and peripheral B- and T-cell phenotypes in 47 previously reported and 5 unreported patients with DADA2. Levels of 21 cytokines and chemokines were quantified in patients with or without anti-TNF treatment. To characterize the DADA2 immune architecture, we performed T- and B-cell receptor immunosequencing. We trained a binary LightGBM classifier to distinguish DADA2 T- and B-cell immune repertoires from healthy individuals.</div></div><div><h3>Results</h3><div>We detected hypogammaglobulinemia in 65% of patients with DADA2 (34 of 52) and cytopenias in 48% (25 of 52). Flow cytometric profiling revealed contraction of B- and T-cell memory compartments. In addition, we observed elevated levels of TNF, IL-8, several interferons, a proliferation-inducing ligand (APRIL), B-cell activating factor (BAFF), and soluble CD40 ligand (sCD40L). High serum levels of TNF, BAFF, and sCD40L persisted under anti-TNF therapy. Next-generation immunosequencing of peripheral lymphocytes showed restricted T-cell receptor repertoires and B cells, which were particularly skewed toward immunoglobulin heavy chain V4-34 rearrangements. With high accuracy, our machine learning algorithm separated individuals with DADA2 from healthy individuals on the basis of immunogenetic parameters regarding B-cell clone fraction, CDR3 length, and selected Kidera factors.</div></div><div><h3>Conclusions</h3><div>Our findings underscore the significant influence of ADA2 on the adaptive immune system, which results in a highly specific immunogenetic signature in patients with DADA2.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 5","pages":"Pages 1664-1674"},"PeriodicalIF":11.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382590","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":"Critical evaluation of feature importance assessment in proteomic analysis using skin microdialysis","authors":"Yoshiyasu Takefuji PhD","doi":"10.1016/j.jaci.2024.12.1096","DOIUrl":"10.1016/j.jaci.2024.12.1096","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 5","pages":"Page 1681"},"PeriodicalIF":11.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449208","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":"From rare to more common: The emerging role of omics in improving understanding and treatment of severe inflammatory and hyperinflammatory conditions","authors":"Salla Keskitalo PhD ,&nbsp;Mikko R.J. Seppänen MD, PhD ,&nbsp;Antonio del Sol PhD ,&nbsp;Markku Varjosalo PhD","doi":"10.1016/j.jaci.2025.02.011","DOIUrl":"10.1016/j.jaci.2025.02.011","url":null,"abstract":"<div><div>Inflammation is a pathogenic driver of many diseases, including atherosclerosis and rheumatoid arthritis. Hyperinflammation can be seen as any inflammatory response that is deleterious to the host, regardless of cause. In medicine, hyperinflammation is defined as severe, deleterious, and fluctuating systemic or local inflammation with presence of a cytokine storm. It has been associated with rare autoinflammatory disorders. However, advances in omics technologies, including genomics, proteomics, and metabolomics, have revealed it to be more common, occurring in sepsis and severe coronavirus disease 2019. With a focus on proteomics, this review highlights the key role of omics in this shift. Through an exploration of research, we present how omics technologies have contributed to improved diagnostics, prognostics, and targeted therapeutics in the field of hyperinflammation. We also discuss the integration of advanced technologies, multiomics approaches, and artificial intelligence in analyzing complex datasets to develop targeted therapies, and we address their potential for revolutionizing the clinical aspects of hyperinflammation. We emphasize personalized medicine approaches for effective treatments and outline challenges, including the need for standardized methodologies, robust bioinformatics tools, and ethical considerations regarding data privacy. This review aims to provide a comprehensive overview of the molecular mechanisms underpinning hyperinflammation and underscores the potential of omics technologies in enabling successful clinical management.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 5","pages":"Pages 1435-1450"},"PeriodicalIF":11.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468183","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":"Evaluating hypogammaglobulinemia after CD19 CAR T-cell therapy","authors":"Pui-Ying Leong MD ,&nbsp;Poi Kuo BA ,&nbsp;James Cheng-Chung Wei MD, PhD","doi":"10.1016/j.jaci.2025.02.019","DOIUrl":"10.1016/j.jaci.2025.02.019","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 5","pages":"Pages 1687-1688"},"PeriodicalIF":11.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634020","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":"Is dupilumab use in atopic dermatitis associated with cutaneous T-cell lymphoma?","authors":"Peck Y. Ong MD","doi":"10.1016/j.jaci.2025.02.002","DOIUrl":"10.1016/j.jaci.2025.02.002","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 5","pages":"Pages 1481-1482"},"PeriodicalIF":11.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425382","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":"CME Calendar-AAAAI","authors":"","doi":"10.1016/S0091-6749(25)00341-0","DOIUrl":"10.1016/S0091-6749(25)00341-0","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 5","pages":"Pages A35-A36"},"PeriodicalIF":11.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143903700","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}