Journal of Allergy and Clinical Immunology最新文献

{"title":"Integrating Geospatial Data With Birth Cohorts to Explore Social Determinants of Health and Asthma.","authors":"Patrick H Ryan,Jeff Blossom,Cole Brokamp,Antonella Zanobetti,Diane R Gold","doi":"10.1016/j.jaci.2025.04.001","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.04.001","url":null,"abstract":"Place-based measures of environmental exposures, climate, neighborhood characteristics, housing, and other social determinants of health (SDoH) are powerful predictors of health outcomes, including asthma. In addition, SDoH are likely causes of the persistent racial and ethnic disparities in asthma prevalence and morbidity. The objectives of this commentary are to 1) provide an overview of geospatial data and resources available to researchers to incorporate into studies of asthma-related outcomes, 2) provide a general approach to consider geospatial data in birth cohorts, 3) demonstrate the use of geospatial data in asthma-related research, and 4) highlight challenges and future opportunities for the use of geospatial data in asthma-related research and birth cohort studies. By integrating place-based data into longitudinal studies, researchers may identify critical drivers of asthma and asthma-related disparities and develop strategies to mitigate their impact.","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"23 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143831545","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":"Advancing birth cohort studies using administrative and other research-independent data repositories - opportunities and challenges.","authors":"Steven M Brunwasser,Allison K Warner,Christian Rosas Salazar,Pingsheng Wu","doi":"10.1016/j.jaci.2025.04.002","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.04.002","url":null,"abstract":"The birth cohort study design is an essential epidemiological tool for investigating the developmental origins of health and disease. Birth cohorts have greatly improved the etiological understanding of asthma and allergic diseases, setting the stage for advancements in translational interventions. Increasingly, investigators leverage data repositories collected and maintained independently of research investigations (administrative data) to establish large birth cohorts or to augment data generated through active participant interaction. In many cases, administrative data can greatly enhance the capacity of birth cohorts to achieve their scientific goals. However, investigators must be wary of common pitfalls and carefully consider whether administrative data is well-suited to the scientific inquiry. This paper reviews the strengths and challenges of using administrative data and pragmatic solutions that have been developed to optimize their use in birth cohorts. As birth cohorts continue to play an important role in understanding early life disease etiology, unleashing the power of administrative data will greatly assist in this scientific process.","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"13 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143831666","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":"CAR therapies: development, design, and implementation.","authors":"Madeline J Lee,Frank Cichocki,Jeffrey S Miller","doi":"10.1016/j.jaci.2025.04.005","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.04.005","url":null,"abstract":"Chimeric antigen receptor (CAR) T and NK cell therapies represent a promising strategy for the treatment of cancers and other chronic diseases. Engineered CAR constructs endow immune cells with the ability to target desired antigens with high specificity, allowing for directed responses to antigen-expressing cells. CAR T and NK cells have shown marked success in the treatment of hematological malignancies, although there remains a large population of patients that fail to respond to CAR therapies and their efficacy in solid tumors is still limited. In this review, we provide a broad overview of the development, design, and implementation of CAR therapies, from bench to bedside. We discuss the building blocks of CAR constructs and how these can be manipulated to optimize CAR functionality, review the possible sources of T and NK cells for CAR therapies, and examine the limitations of both CAR T and CAR NK cells. Finally, we discuss recent breakthroughs in the CAR field and consider how these advances may impact the success of CAR therapies in the years to come.","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"90 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827109","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":"Effects of Inflammatory Endotypes on Disease Trajectory in Chronic Rhinosinusitis with Nasal Polyps.","authors":"Christina Dorismond,Yash Trivedi,Mason R Krysinski,Rory J Lubner,Li-Ching Huang,Sandeep Goswami,Quanhu Sheng,Rakesh K Chandra,Naweed I Chowdhury,Justin H Turner","doi":"10.1016/j.jaci.2025.03.029","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.03.029","url":null,"abstract":"BACKGROUNDWhile phenotypic features have traditionally guided treatment in chronic rhinosinusitis (CRS), recent research has favored categorization based on inflammatory endotype. However, the impact of endotypic differences on clinical outcomes remains largely unknown.OBJECTIVEWe aimed to compare disease trajectory, primarily time-to-polyp recurrence, between CRS with nasal polyp (CRSwNP) endotypes.METHODSSamples were obtained from CRSwNP patients undergoing surgery between 2015-2023, and cytokine levels were measured using a multiplex bead assay. Principal component analysis followed by hierarchical cluster analysis was used to identify endotype clusters. Clinical outcomes were subsequently compared between clusters RESULTS: We identified 6 CRSwNP disease clusters among the 269 included patients. Cluster 1 (46.5%) was characterized by relatively low inflammation. Clusters 4 (13.3%) and 6 (7.1%) also exhibited low inflammation but with elevated levels of interleukin (IL)-12/IL-21 and CCL5, respectively. Cluster 2 (4.5%) represented a mixed type 1/3 inflammatory endotype (IFN-γHigh/IL-4High/IL-17AHigh), and Cluster 3 (10.0%) was characterized by an innate, proinflammatory response (IL-1βHigh/IL-6High/IL-8High). Cluster 5 (18.9%) exhibited type 2 dominant inflammation (IL-5High/IL-9High/IL-13High). When comparing disease trajectory, Cluster 2 (IFN-γHigh/IL-4High/IL-17AHigh) and 4 (IL-12High/IL-21High) had the shortest time-to-polyp recurrence, while Cluster 3 (IL-1βHigh/IL-6High/IL-8High) demonstrated the longest time-to-recurrence (p<0.001). Time-to-oral steroids (p=0.13) and time-to-biologic therapy (p=0.43) were similar across clusters CONCLUSION: Our study highlights the heterogenous nature of CRSwNP and differences in disease trajectory between endotypes, notably that patients with mixed type 1 and 3 inflammation demonstrate more recalcitrant disease. These findings suggest that therapies beyond traditional type 2 inflammation treatments may be needed to effectively reduce CRSwNP disease recurrence.","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"183 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827107","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":"A New Era for Complement Therapeutics.","authors":"Trent M Woodruff","doi":"10.1016/j.jaci.2025.04.006","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.04.006","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"21 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827110","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":"Endotypes of Chronic Spontaneous Urticaria and Angioedema.","authors":"Dennis Wong,Susan Waserman,Gordon L Sussman","doi":"10.1016/j.jaci.2025.04.004","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.04.004","url":null,"abstract":"The current understanding of chronic spontaneous urticaria (CSU) suggests that a complex network of inflammatory pathways is involved in its pathogenesis. Recent development highlighted autoimmunity as one of the key pathogenic mechanisms of CSU. Two endotypes, type I autoallergic (associated with IgE antibodies against autoantigens) and type IIb autoimmune (mediated by IgG autoantibodies against IgE or its high affinity receptor (FcεRI), have been characterized. A subpopulation of the patients has an overlap of the two endotypes. About 10% of patients with CSU presents with angioedema only. Patients with isolated mast-cell mediated angioedema have distinct clinical and demographic features and should be distinguished from bradykinin-mediated angioedema. Multiple potential biomarkers such as total IgE level and IgG anti-thyroid peroxidase have been identified, and together with the corresponding endotypes, have been linked to disease severity, duration and response to treatments. Currently, the utility of these biomarkers is limited in clinical settings given the few options of therapy. However, with the advent of novel treatments, endotyping CSU might help with tailoring treatment approach.","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"6 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827112","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":"LRBA functional deficiency caused by biallelic LRBA missense variants characterized by Evans syndrome or colitis.","authors":"Samuel Cc Chiang,Li Yang,Erika Owsley,Ammar Husami,Nagako Akeno,Cristina Cobb,Nicholas L Hartog,Araceli Elizalde,Christine M Seroogy,Geraldine Blanchard-Rohner,Xiao P Peng Md,Rae Brager,David Buchbinder,Eleanor Cook,Lindsay Phillips,Snezana Maricic,Tatiana Kalashnikova,Beata Derfalvi,Victoria R Dimitriades,Luis E Murguía-Favela,Maria J Gutierrez,Anitha Shrikhande,MacGregor Steele,Jo L Wilson,Nicola Am Wright,Rebecca Marsh,Jack Bleesing,Michael B Jordan,Ashish K Marwaha BMBch","doi":"10.1016/j.jaci.2025.04.003","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.04.003","url":null,"abstract":"BACKGROUNDBiallelic loss-of-function (LOF) mutations in LRBA (lipopolysaccharide-responsive and beige-like anchor) lead to a severe syndrome of early-onset immune dysregulation called LRBA deficiency. Monoallelic CTLA4 mutations lead to a similar phenotype. In both conditions, Treg CTLA-4 levels are significantly decreased. In previously reported cases of symptomatic disease associated with LRBA pathogenic variants, patients usually have severely decreased or absent LRBA protein levels.OBJECTIVEWe describe here five patients with biallelic missense variants in the LRBA gene presenting predominantly with Evans syndrome or colitis.METHODSLRBA and CTLA-4 levels were investigated in LRBA missense, \"classic\" LRBA, and CTLA-4 insufficiency samples.RESULTSSurprisingly, all five LRBA missense patients have normal expression of LRBA protein. However, CTLA-4 intracellular expression was reduced to similar levels as those seen in CTLA-4 insufficiency patients at resting state. Lower levels of surface CTLA-4 are seen upon cell activation, indicating that these LRBA variants lead to reduced CTLA-4 cell surface expression. Several of the missense variants are shared between unrelated patients in the cohort suggesting a mutational hotspot or founder effect for those with shared ancestry.CONCLUSIONHerein, we describe novel LRBA deficiency variants resulting in quantitative or qualitative LRBA defects, leading to reduced intracellular resting levels and induced surface levels of CTLA-4.","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"6 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827121","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":"Personalised therapeutic approaches for asthma.","authors":"Ioana Agache, Ian M Adcock, Federico Baraldi, Kian Fan Chung, Ibon Eguiluz-Gracia, Sebastian L Johnston, Marek Jutel, Parameswaran Nair, Alberto Papi, Celeste Porsbjerg, Omar S Usmani, Deborah A Meyers, Magdalena Zemelka-Wiacek, Eugene R Bleecker","doi":"10.1016/j.jaci.2025.03.025","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.03.025","url":null,"abstract":"<p><p>Differences in host susceptibility and environmental exposures result in significant heterogeneity in asthma clinical expression, natural evolution and response to treatment. These differences are influenced by many factors including genomics, epigenomics, transcriptomics, proteomics and metabolomics, many of which are modified by environmental and allergic exposures. The complex and multiple characteristics that interact in asthma development and progression pose significant challenges for personalized management. This review aims to guide the clinician in its management decisions by reviewing each of the components important in developing this therapeutic paradigm and by providing several integrated goals for precision or personalized medicine for asthma. Biologic characteristics of asthma in relation to the genomics, exposome and hypersensitivity reactions (allergic responsiveness) resulting in the asthma diathesis are discussed. Further insights including the use of targeted biologics and allergen immunotherapy are provided, while discussing the importance of targeting the epithelium, mucus production, airway smooth muscle and the small airways. We examine the value of multivariate cluster analyses as a new paradigm that can inform treatment decisions and the potential of adaptive trial design to evaluate known and novel predictive biomarkers and characterize disease heterogeneity.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143999904","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":"Inside job: Roles of intracellular C3.","authors":"Behdad Afzali, Parul Singh, Md Tajmul, Claudia Kemper","doi":"10.1016/j.jaci.2025.03.024","DOIUrl":"10.1016/j.jaci.2025.03.024","url":null,"abstract":"<p><p>Our understanding of the complement system continues to grow beyond that of a liver-derived systemically operative mechanism of pathogen clearance to a central orchestrator of single-cell behavior and tissue biology. These expanded activities reflect the extrahepatic and local production of complement by many, if not most, cells, and the unexpected recent finding that complement also serves important physiological intracellular roles. The complement core component C3 has emerged as a particularly critical player in basic cell functions. Here, we provide an overview of the currently known forms and functions of intracellular C3 and the mechanisms that control it. We also discuss 2 emerging concepts as potential key areas for future exploration: intracellular C3 as a second layer of pathogen defense at host-environmental interfaces and \"C3 licensing.\" We conclude by suggesting that the potential clinical implications surrounding perturbations in intracellular C3 activities should be explored better.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803551","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":"Nasal transcriptome differences preceding recurrent wheezing in infancy.","authors":"Poshmaal Dhar, Martin O'Hely, Luba Sominsky, Sarah Ashley, Sarath C Ranganathan, Peter D Sly, Fiona Collier, Mimi L K Tang, Rachel Morgan, Toby Mansell, Richard Saffery, David Burgner, Anne-Louise Ponsonby, Peter Vuillermin","doi":"10.1016/j.jaci.2025.03.021","DOIUrl":"10.1016/j.jaci.2025.03.021","url":null,"abstract":"<p><strong>Background: </strong>Mucosal immune responses and epithelial barrier function are key emerging determinants of susceptibility to wheezing illnesses in early life.</p><p><strong>Objective: </strong>We sought to investigate the association between nasal transcriptome in healthy infants and the subsequent incidence of recurrent wheeze.</p><p><strong>Methods: </strong>In a population-derived prebirth cohort study, whole-transcriptome sequencing was performed to compare the nasal transcriptome at 1 month of age from 26 infants who subsequently developed recurrent wheeze (parents' record in symptom diary) in the first year of life with that of 22 infants who remained wheeze-free. Differentially expressed genes (DEGs) were identified using DEseq2, followed by overrepresentation pathway (Gene Ontology [GO] and Kyoto Encyclopedia of Genes and Genomes) and upstream regulator analyses (Ingenuity Pathway Analysis).</p><p><strong>Results: </strong>A total of 202 DEGs (false discovery rate ≤ 0.1 and absolute log2 fold change > 1; 66 upregulated and 136 downregulated) were associated with recurrent wheeze. Upregulated GO pathways associated with recurrent wheeze included chemokine-mediated signaling and eosinophil and monocyte chemotaxis. The downregulated GO included cilium organization and cellular aldehyde metabolic process. TNF emerged as the key driver (adjusted P value and z score) of DEG patterns in the recurrent wheeze group, with OSMR and IL21 identified as master regulators.</p><p><strong>Conclusion: </strong>The nasal transcriptome in early infancy is associated with subsequent recurrent wheezes, indicating upregulation of immune cell chemotaxis, decreased epithelial barrier function, and altered cilium organization and mitochondrial function. Future studies are required to evaluate the use of nasal transcriptome in the early detection of infants at risk of recurrent wheeze and to generate new knowledge of antecedent pathways as targets for novel primary prevention strategies.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795323","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}