Journal of Allergy and Clinical Immunology最新文献

{"title":"Evaluating hypogammaglobulinemia after CD19 CAR T-cell therapy.","authors":"Pui-Ying Leong, Poi Kuo, James Cheng-Chung Wei","doi":"10.1016/j.jaci.2025.02.019","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.02.019","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-03-14","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":"IRF2BP2 Deficiency: An important form of common variable immunodeficiency with inflammation.","authors":"Chioma Udemgba, Bethany Pillay, Samantha Shafer, Angelika Alberstadt, Michael Abers, Olivier Gilliaux, Karin Chen, William Rae, Leif Hanitsch, Horst Von Bernuth, Joao Farela Neves, Nikita Raje, Leen Moens, P Martin van Hagen, Jenna Bergerson, Nicholas Hartog, Tim Niehues, Gregor Dückers, Emilia Falcone, Michael Keller, Amy Hsu, Isabelle Meyts, Steven M Holland","doi":"10.1016/j.jaci.2025.02.038","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.02.038","url":null,"abstract":"<p><strong>Background: </strong>Interferon regulatory factor-2 binding protein-2 (IRF2BP2) is a transcription factor that plays an important role in regulating immune pathways, angiogenesis, apoptosis, and cell differentiation. Defects in this gene have been implicated in immunodeficiency.</p><p><strong>Objective: </strong>To deepen the understanding of the clinical implications of IRF2BP2 variants, we sought to clinically characterize and functionally test thirty-four individuals with IRF2BP2 variants.</p><p><strong>Methods: </strong>We collected 34 subjects across 18 families with mutations in IRF2BP2. Records were abstracted for clinical phenotypes. Functional testing was performed on peripheral blood mononuclear cells (PBMCs). Nuclear factor of activated T cells (NFAT) luciferase gene reporter constructs and quantitative cDNA determinations were used to evaluate repressor activity associated with ectopic expression of various IRF2BP2 mutant constructs in Jurkat cells.</p><p><strong>Results: </strong>Most subjects had immunodeficiency (91%, n = 30/33) with variable gastrointestinal (65%, n= 20/31) and inflammatory or autoimmune features (57%, n=17/30), including chronic abdominal pain, colitis, diarrhea, constipation, vitiligo, alopecia, and migratory rashes. There was a reduced frequency of memory B-cells with poor immunoglobulin production and reduced calcium flux in response to B-cell receptor stimuli. PBMCs had increased apoptosis in vitro compared to healthy controls. Impaired IRF2BP2 repression of NFAT activation was observed using patient-derived mutant IRF2BP2 constructs compared to wild-type. Similarly, TNF-α transcript levels were higher using patient-derived mutations compared to wild-type IRF2BP2 constructs.</p><p><strong>Conclusions: </strong>IRF2BP2 deficiency causes a complex immunodeficiency including gastrointestinal and inflammatory disorders as well as impaired B-cell maturation. Impaired repression of the NFAT pathway appears to enhance proinflammatory signaling through proinflammatory cytokine expression.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639506","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":"Reply.","authors":"Chang-Gyu Jung, Seong Ho Cho","doi":"10.1016/j.jaci.2025.02.010","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.02.010","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634022","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":"Upper airway comorbidities of asthma in patients with aspirin-exacerbated respiratory disease.","authors":"Piotr Szatkowski, Lucyna Mastalerz","doi":"10.1016/j.jaci.2025.02.009","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.02.009","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634024","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":"Reply.","authors":"Natalia M Sutherland, Sara Barmettler","doi":"10.1016/j.jaci.2025.02.020","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.02.020","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634023","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":"Basophil-VAMP7 is a vital regulator of skin barrier integrity and chronic itch.","authors":"Wenhao Zhang, Xiaolong Dai, Weiwei Chen, Yanqing Li, Huiyuan Mei, Jorg Buddenkotte, Xingyun Zhu, Martin Steinhoff, Jiafu Wang, Jianghui Meng","doi":"10.1016/j.jaci.2025.02.035","DOIUrl":"10.1016/j.jaci.2025.02.035","url":null,"abstract":"<p><strong>Background: </strong>Atopic dermatitis (AD) is a multifaceted inflammatory skin disease characterized by chronic itch and acute itch flare (AIF), with basophils playing pivotal roles in both. VAMP7 mediates immune responses; however, its function in basophils remains undefined.</p><p><strong>Objective: </strong>We sought to elucidate the role of VAMP7 in basophil-mediated chronic itch and AIF in AD.</p><p><strong>Methods: </strong>Basophil-specific VAMP7 knockout (Ba-V7KO) and control V7^fl/fl mice were used to model chronic itch and AIF in AD. The role of basophil-VAMP7 was assessed through RNA sequencing, fluorescence-activated cell sorting, quantitative RT-PCR, ELISA, and pharmacological inhibition.</p><p><strong>Results: </strong>Ba-V7KO mice exhibited impaired chronic itch but normal AIF, accompanied by reduced skin levels of MCPT8, histamine, CCL24, and CCR3 across both models, whereas OSM was reduced only in the AIF model. After fluorescence-activated cell sorting, VAMP7 knockout basophils exhibited reduced activity, with OSM downregulated in AIF and CCR3 reduced in both models. VAMP7 knockout also decreased IL-4 and LTC₄ release from basophils. Additionally, OSM downregulated barrier proteins and upregulated pruriceptors in keratinocytes; however, these effects were reversed by SC144, which restored skin barrier function in AIF without affecting itch response in either model. In the chronic model, CCR3 inhibition alleviated pruritus, correlating with the downregulation of itch-related transcripts.</p><p><strong>Conclusion: </strong>VAMP7 is essential for basophil-driven chronic itch and AIF in AD by maintaining basophil activity, regulating skin barrier damage in AIF via the OSM pathway, and modulating chronic itch through the CCL24/CCR3 axis. Targeting basophil-VAMP7 offers a potential strategy to restore skin barrier function in AIF and alleviate chronic itch in AD.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633856","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":"Child Opportunity Index at birth and asthma with recurrent exacerbations in the US ECHO program.","authors":"Rachel L Miller, Holly Schuh, Aruna Chandran, Rima Habre, Jyoti Angal, Izzuddin M Aris, Judy L Aschner, Casper G Bendixsen, Jeffrey Blossom, Michelle Bosquet-Enlow, Carrie V Breton, Carlos A Camargo, Kecia N Carroll, Sarah Commodore, Lisa A Croen, Dana M Dabelea, Sean C L Deoni, Assiamira Ferrara, Rebecca C Fry, Jody M Ganiban, Sarah D Geiger, James E Gern, Frank D Gilliland, Semsa Gogcu, Diane R Gold, Marion E Hare, Robyn N Harte, Tina V Hartert, Irva Hertz-Picciotto, Alison E Hipwell, Daniel J Jackson, Margaret K Karagas, Gurjit K Khurana Hershey, Haejin Kim, Augusto A Litonjua, Carmen J Marsit, Cynthia T McEvoy, Eneida A Mendonça, Paul E Moore, Anh P Nguyen, Flory L Nkoy, Thomas G O'Connor, Emily Oken, Dennis R Ownby, Matthew Perzanowski, Katherine Rivera-Spoljaric, Sheela Sathyanarayana, Anne Marie Singh, Joseph B Stanford, Annemarie Stroustrup, Nissa Towe-Goodman, Veronica A Wang, Tracey J Woodruff, Robert O Wright, Rosalind J Wright, Antonella Zanobetti, Edward M Zoratti, Christine C Johnson","doi":"10.1016/j.jaci.2025.02.036","DOIUrl":"10.1016/j.jaci.2025.02.036","url":null,"abstract":"<p><strong>Background: </strong>Environmental exposures and social determinants likely influence specific childhood asthma phenotypes.</p><p><strong>Objective: </strong>We hypothesized that the Child Opportunity Index (COI) at birth, measuring multiple neighborhood opportunities, influences incidence rates (IRs) for asthma with recurrent exacerbations (ARE).</p><p><strong>Methods: </strong>We tested for COI associations with ARE IRs in 15,877 children born between 1990 and 2018 in the ECHO (Environmental Influences on Child Health Outcomes) program. Parent-reported race and ethnicity and other demographics were assessed as effect modifiers.</p><p><strong>Results: </strong>The IRs of ARE for children born in very low COI neighborhoods was higher (IR = 10.98; 95% CI: 9.71, 12.25) than for other COI categories. Rates for non-Hispanic Black (NHB) children were significantly higher than non-Hispanic White children in every COI category. The ARE IRs for children born in very low COI neighborhoods were several-fold higher for NHB and Hispanic Black children (IR = 15.30; 95% CI: 13.10, 17.49; and IR = 18.48; 95% CI: 8.80, 28.15, respectively) when compared to White children. Adjusting for individual-level characteristics, children born in very low COI neighborhoods demonstrated an ARE IR ratio of 1.26 (95% CI: 0.99, 1.59) with a higher incidence of cases among children ages 2 to 4 years and with a parental history of asthma.</p><p><strong>Conclusions: </strong>Rates of ARE were higher among children born in under-resourced communities, and this relationship is strongest for young minoritized children with a parental history of asthma. Higher rates for NHB even in the highest COI categories suggest that risk associated with race persists regardless of social disadvantage.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634019","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":"Plasma pharmacometabolomics of inhaled corticosteroid-related adrenal suppression in asthma.","authors":"Dung T Tran, Yulu Chen, Lourdes G Ramirez, Jessica A Lasky-Su, Ann C Wu, Kelan G Tantisira, Michael J McGeachie, Scott T Weiss, Amber Dahlin","doi":"10.1016/j.jaci.2025.02.037","DOIUrl":"10.1016/j.jaci.2025.02.037","url":null,"abstract":"<p><strong>Background: </strong>Inhaled corticosteroids (ICSs) are frequently prescribed medications for asthma symptoms, but higher doses can increase risks of adrenal insufficiency through suppression of endogenous cortisol production. Understanding which patients may be at increased risk for developing adrenal suppression related to ICS use may help providers improve treatment regimens for asthmatic patients; however, the mechanisms underlying ICS-related adrenal insufficiency have not been clarified.</p><p><strong>Objective: </strong>We sought to identify metabolite signatures and biochemical pathways associated with ICS-related adrenal insufficiency in asthmatic patients.</p><p><strong>Methods: </strong>Global metabolite profiling (metabolomics) was integrated with electronic medical records data including the development of adrenal suppression in 2 independent asthma cohorts. The discovery cohort (Pharmacogenomics of Adrenal Suppression with Inhaled Corticosteroids) included 711 adult asthmatic patients on ICSs. Untargeted metabolomic profiling identified 1397 metabolites, of which 810 were selected for further analysis. Using plasma cortisol as a biomarker for adrenal status (outcome), linear regression models were used to identify associations between metabolites and plasma cortisol, adjusted for potential confounders. In the validation cohort (Omics Determinant of Longitudinal Lung Function in Asthma Study), metabolite associations were validated in 575 patients on ICSs. Pathway and network analyses were performed using bioinformatic approaches to identify altered metabolic pathways related to the outcome.</p><p><strong>Results: </strong>Of 810 endogenous metabolites, 12 demonstrated significant associations with adrenal insufficiency after correction for multiple comparisons. In the validation cohort, 3 of these 12 replicated, including 2 steroid metabolites (tetrahydrocortisol glucuronide and tetrahydrocortisol glucuronide (5)) and homocitrulline. Pathway and network analyses revealed alterations in biochemical pathways related to the metabolism of steroids, bile acids, urea cycle, and long-chain polyunsaturated fatty acids.</p><p><strong>Conclusions: </strong>We have identified specific metabolites within steroid and nonsteroid metabolic pathways that are associated with adrenal insufficiency with ICS use.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634021","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":"Identifying allergic and nonallergic type 2 asthma endotypes: Moving beyond blood eosinophil counts and fractional exhaled nitric oxide.","authors":"Ian M Adcock, Sharon Mumby, Trevor T Hansel","doi":"10.1016/j.jaci.2025.03.003","DOIUrl":"10.1016/j.jaci.2025.03.003","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630302","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 normal, the abnormal, and the at risk: How can old and new birth cohort studies help?","authors":"Yukiko Kunitomo, Meredith C McCormack, Andrew Bush","doi":"10.1016/j.jaci.2025.03.004","DOIUrl":"10.1016/j.jaci.2025.03.004","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630339","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}