Journal of Allergy and Clinical Immunology最新文献

{"title":"Direct epitope study using human IgE mAbs against peanut allergens","authors":"Hirohisa Saito MD, PhD , Masato Tamari MD, PhD , Tatsuki Fukuie MD, PhD , Kenji Matsumoto MD, PhD , Hideaki Morita MD, PhD","doi":"10.1016/j.jaci.2025.02.021","DOIUrl":"10.1016/j.jaci.2025.02.021","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 5","pages":"Pages 1483-1485"},"PeriodicalIF":11.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537157","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":"Antibody-secreting cell repertoires hold high-affinity anti-rocuronium specificities that can induce anaphylaxis in vivo","authors":"Alice Dejoux PhD ,&nbsp;Qianqian Zhu PhD ,&nbsp;Adam Woolfe PhD ,&nbsp;Ophélie Godon MS ,&nbsp;Sami Ellouze ,&nbsp;Guillaume Mottet PhD ,&nbsp;Carlos Castrillon PhD ,&nbsp;Caitlin Gillis PhD ,&nbsp;Cyprien Pecalvel ,&nbsp;Christelle Ganneau ,&nbsp;Bruno Iannascoli ,&nbsp;Frédéric Lemoine PhD ,&nbsp;Frederick Saul PhD ,&nbsp;Patrick England PhD ,&nbsp;Laurent L. Reber PhD ,&nbsp;Aurélie Gouel-Chéron MD, PhD ,&nbsp;Luc de Chaisemartin PharmD, PhD ,&nbsp;Ahmed Haouz PhD ,&nbsp;Gaël A. Millot PhD ,&nbsp;Sylvie Bay PhD ,&nbsp;Pierre Bruhns PhD","doi":"10.1016/j.jaci.2025.01.025","DOIUrl":"10.1016/j.jaci.2025.01.025","url":null,"abstract":"<div><h3>Background</h3><div>Neuromuscular blocking agents (NMBAs) are muscle relaxants used to assist mechanical ventilation but lead in 1 per 10,000 anesthesia cases to severe acute hypersensitivity reactions—that is, anaphylaxis. Incidences vary between types of NMBAs. Rocuronium, a widely used nondepolarizing aminosteroid NMBA, induces among the highest anaphylaxis rates. Rocuronium-induced anaphylaxis is proposed to rely on preexisting rocuronium-binding antibodies, but no such antibodies have ever been identified.</div></div><div><h3>Objectives</h3><div>We sought to identify rocuronium-specific antibody repertoires from plasma cells or plasmablasts of rocuronium-immunized mice to determine the affinities, structures, and anaphylactogenic potential of these antibodies for rocuronium.</div></div><div><h3>Methods</h3><div>We engrafted rocuronium onto carrier proteins allowing immunization of mice against rocuronium, screening for rocuronium-specific antibody responses, and sorting of rocuronium-specific plasma cells using droplet microfluids coupled to single-cell antibody gene (variable heavy chain [VH] and variable light chain [VL]) sequencing.</div></div><div><h3>Results</h3><div>The 2 different repertoires of &gt;500 VH-VL pairs were oligoclonal, comprised 3 major clonal families, and displayed convergence. Expressed as human IgG1, these antibodies demonstrated subnanomolar affinities for rocuronium with families either monospecific for rocuronium or cross-reactive only for closely related NMBAs. Expressed as human IgE, they triggered human mast cell and basophil activation, and severe passive systemic anaphylaxis in mice humanized for the IgE receptor FcεRI. Cocrystal structures between rocuronium and antibody representatives of 3 different VH-VL families revealed distinct interaction modes, with the ammonium group involved systematically in the binding interface.</div></div><div><h3>Conclusions</h3><div>This work identifies the epitopes of antibody reactivity to rocuronium, demonstrates anaphylactogenic potential of anti-rocuronium IgE, and establishes the first mouse model of NMBA anaphylaxis.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 5","pages":"Pages 1557-1574"},"PeriodicalIF":11.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074485","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":"Sputum short-chain fatty acids, microbiome, inflammation, and mucus plugging in obstructive airway disease","authors":"Naoya Tanabe MD, PhD ,&nbsp;Hisako Matsumoto MD, PhD ,&nbsp;Chie Morimoto MD, PhD ,&nbsp;Toyohiro Hirai MD, PhD","doi":"10.1016/j.jaci.2025.01.031","DOIUrl":"10.1016/j.jaci.2025.01.031","url":null,"abstract":"<div><h3>Background</h3><div>Short-chain fatty acids (SCFAs), produced by anaerobic bacteria through fermentation in the gut, may suppress eosinophilic inflammation while potentially promoting neutrophilic inflammation. However, the role of local SCFAs in the airway microbiome, inflammation, and mucus plugging in type 2–dominant obstructive airway diseases remains unclear.</div></div><div><h3>Objective</h3><div>Our aim was to investigate associations between sputum SCFAs and the relative abundance of anaerobic bacteria, neutrophil and eosinophil counts in sputum, and mucus plug scores on computed tomography images in patients with obstructive airway diseases.</div></div><div><h3>Methods</h3><div>Sputum samples and chest computed tomography images were prospectively collected in stable patients with asthma with fixed airflow limitation, chronic obstructive pulmonary disease, and asthma–chronic obstructive pulmonary disease overlap (ACO). Sputum samples were analyzed for concentrations of SCFA, including n-butyrate, acetate, and propionate; microbiome composition using 16S rRNA sequencing; and inflammatory cell differentials.</div></div><div><h3>Results</h3><div>In 46 patients, enriched for ACO with relatively high levels of type 2 markers, higher SCFA levels were associated with higher relative abundance of bacteria of the phylum Bacteroidetes and lower relative abundance of bacteria of the phylum Proteobacteria. Hierarchic clustering identified a severe eosinophil-dominant inflammation cluster characterized by lower SCFAs levels and higher mucus plug scores. In the 2 neutrophilic clusters, one characterized by higher SCFAs levels and the other by lower SCFAs levels, lower butyrate levels were significantly associated with higher mucus plug scores.</div></div><div><h3>Conclusion</h3><div>Local SCFA concentrations may be closely associated with the airway microbiome and influence mucus plugging in ACO-enriched populations. Understanding these interactions could inform therapeutic strategies targeting SCFAs or the microbiome to manage type 2–dominant obstructive airway diseases.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 5","pages":"Pages 1675-1680"},"PeriodicalIF":11.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364778","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":"Closing in on epithelial barrier dysfunction in chronic rhinosinusitis","authors":"Nora A. Barrett MD","doi":"10.1016/j.jaci.2025.02.039","DOIUrl":"10.1016/j.jaci.2025.02.039","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 5","pages":"Pages 1478-1480"},"PeriodicalIF":11.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692198","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":"Rhinoconjunctivitis symptoms in children and adolescents with asthma: Longitudinal clustering analysis","authors":"Alkis Togias MD ,&nbsp;Peter J. Gergen MD ,&nbsp;Andrew H. Liu MD ,&nbsp;Haejin Kim MD ,&nbsp;Robert A. Wood MD ,&nbsp;George T. O’Connor MD ,&nbsp;Melanie Makhija MD ,&nbsp;Gurjit K. Khurana Hershey MD, PhD ,&nbsp;Carolyn M. Kercsmar MD ,&nbsp;Rebecca S. Gruchalla MD, PhD ,&nbsp;Carin Lamm MD ,&nbsp;Leonard B. Bacharier MD ,&nbsp;Shilpa J. Patel MD, MPH ,&nbsp;James E. Gern MD ,&nbsp;Daniel J. Jackson MD ,&nbsp;Cynthia M. Visness PhD ,&nbsp;Agustin Calatroni MS ,&nbsp;William W. Busse MD","doi":"10.1016/j.jaci.2024.12.1084","DOIUrl":"10.1016/j.jaci.2024.12.1084","url":null,"abstract":"<div><h3>Background</h3><div>Rhinoconjunctivitis phenotypes are conventionally described on the basis of symptom severity, duration and seasonality, and aeroallergen sensitization. It is not known whether these phenotypes fully reflect the patterns of symptoms seen at a population level.</div></div><div><h3>Objective</h3><div>We sought to identify phenotypes of rhinoconjunctivitis on the basis of symptom intensity and seasonality using an unbiased approach and to compare their characteristics.</div></div><div><h3>Methods</h3><div>A cohort of children with asthma in low-income urban environments was prospectively followed with a rhinoconjunctivitis activity questionnaire, and their upper and lower airway disease was managed for 12 months with every 2-month visit based on standardized algorithms. We identified individual rhinoconjunctivitis symptom trajectories and clusters of those trajectories and compared the clusters focusing on atopic characteristics.</div></div><div><h3>Results</h3><div>Data obtained from 619 children yielded 5 symptom clusters: 2 had high symptoms (22.5%) but differed in seasonal pattern, 1 had medium symptoms (13.6%), 1 had medium nasal congestion only (20.4%), and 1 had low symptoms (43.6%). The latter was further split into 2 subgroups if nasal corticosteroids were frequently prescribed (23.6%) or not (20.0%). Seasonal variation was absent in the low symptom clusters. The number of allergic sensitizations and family history of allergic airway disease were higher in the high symptom clusters, but allergic sensitization did not explain differences in seasonality.</div></div><div><h3>Conclusions</h3><div>This study identified rhinoconjunctivitis phenotypes that have not been previously reported and were not differentiated by demographics or by measures of atopy and type 2 inflammation. Factors beyond allergy need to be investigated to better understand the pathobiology of rhinoconjunctivitis.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 5","pages":"Pages 1490-1498.e10"},"PeriodicalIF":11.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927185","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":"Antigenic determinants underlying IgE-mediated anaphylaxis to peanut","authors":"Scott A. Smith MD, PhD ,&nbsp;Yasmin W. Khan MD ,&nbsp;Rebecca A. Shrem BS ,&nbsp;Jonathan A. Hemler MD ,&nbsp;Joshua E. Doyle MS, MSN, FNP-C ,&nbsp;Jacob Daniel MD ,&nbsp;Jian Zhang MS ,&nbsp;Glorismer Pena-Amelunxen BS ,&nbsp;Lorenz Aglas PhD ,&nbsp;Robert G. Hamilton PhD ,&nbsp;Robert Getts PhD ,&nbsp;Hugh A. Sampson MD ,&nbsp;Joyce J.W. Wong PhD ,&nbsp;Derek Croote PhD ,&nbsp;R. Stokes Peebles Jr. MD ,&nbsp;Benjamin W. Spiller PhD","doi":"10.1016/j.jaci.2024.12.1094","DOIUrl":"10.1016/j.jaci.2024.12.1094","url":null,"abstract":"<div><h3>Background</h3><div>Studies of human IgE and its targeted epitopes on allergens have been very limited. We established a method to immortalize IgE-encoding B cells from patients with allergy.</div></div><div><h3>Objective</h3><div>We sought to develop an unbiased and comprehensive panel of peanut-specific human IgE mAbs to characterize key immunodominant antigenic regions and epitopes on peanut allergens to map molecular interactions responsible for inducing anaphylaxis.</div></div><div><h3>Methods</h3><div>Using human hybridoma technology to immortalize IgE-encoding B cells from peripheral blood of subjects with severe peanut allergy, we generated a panel of naturally occurring human IgE mAbs in an unbiased manner. Isolated IgE mAbs were characterized extensively in allergen binding assays, peptide array analysis, antigenic mapping, binding kinetic analysis, serum blocking, skin testing inhibition, and functional assessment using human FCεRI transgenic mice.</div></div><div><h3>Results</h3><div>We created a large panel of 54 peanut-specific IgE mAbs, of which 63% were specific for Ara h 2 and/or Ara h 6. Pairs of IgE mAbs with the same antigen specificity but different binding sites were able to mediate passive systemic anaphylaxis in FCεRI transgenic mice. A single mAb targeting the repetitive motif on Ara h 2 was able to induce degranulation and anaphylaxis on its own. IgG₁ switch variant immunoglobulins of the IgE mAb inhibited binding of 30% to 60% of patients’ IgE to peanut extract (ImmunoCAP) and reduced peanut extract–induced skin wheal sizes by 1.6 to 7.4 mm in patients with peanut allergy.</div></div><div><h3>Conclusion</h3><div>We created a molecular map of the IgE antibody response to the most important peanut allergen proteins to enable the design of new allergy immunotherapies and vaccines.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 5","pages":"Pages 1595-1606.e10"},"PeriodicalIF":11.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142989380","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":"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}