Journal of Allergy and Clinical Immunology最新文献

{"title":"Systemic Allergic Reactions to mRNA COVID-19 Vaccines: A Randomized Placebo-controlled Trial.","authors":"Lisa M Wheatley, James R Baker, N Franklin Adkinson, Rebecca Gruchalla, Charles F Schuler, Deborah A Oberdoerster, Anju T Peters, Gayatri Bhakti Patel, Kimberly G Blumenthal, Anna R Wolfson, Lacey B Robinson, Edward M Zoratti, Haejin Kim, Elizabeth J Phillips, Cosby A Stone, Allison Ramsey, Stacie M Jones, Akilah A Jefferson, Merin Kuruvilla, Maria Garcia-Lloret, Terrie S Ahn, Mariana C Castells, Matthew P Giannetti, Timothy J Craig, Maria P Henao, Thomas B Casale, Amber N Pepper, Bruce J Lanser, Flavia C L Hoyte, Giselle S Mosnaim, Stephanie L Mehlis, David A Khan, Paula J Busse, Lawrence B Schwartz, Sanjiv Sur, Tara F Carr, Magdalena E Sobieszczyk, David B Peden, Mark S Dykewicz, Mary Beth Fasano, Michael R Nelson, Sayantani B Sindher, Mark H Moss, Gary Kleiner, Melanie C Dispenza, Samuel K Lai, Andrew T Lucas, Zhongbo Li, Quang Trong Le, Matthew C Altman, Madison S Cox, Hanno Steen, Saima Ahmed, Arthur Viode, Joanna Pucilowska, Khauan Bainha, Ginger L Milne, Warda Amin, Edward P Feener, Daniel Lee, Manuel D Galvan, James R Busby, Patrick R Romano, Kathleen Schroeder, Gloria David, Agustin Calatroni, Kristen Mason, Michael Nodzenski, Angie Wu, Wesley Storm, Erica Brittain, Caeden Dempsey, Julian Poyser, Sanaz Daneshfar Hamrah, Ling Li, Alkis Togias","doi":"10.1016/j.jaci.2026.09.024","DOIUrl":"https://doi.org/10.1016/j.jaci.2026.09.024","url":null,"abstract":"<p><strong>Background: </strong>COVID-19 mRNA vaccines were associated in early reports with more allergic reactions than most vaccines, especially in people with allergic histories.</p><p><strong>Objective: </strong>To estimate the proportions of systemic allergic reactions to mRNA COVID-19 vaccines in people reporting prior severe allergic reactions to various allergens, and/or mast cell disorders (PSAR/MCD Group) and determine if proportions are higher than in non-PSAR/non-MCD (Comparison Group).</p><p><strong>Methods: </strong>We conducted a multi-center, randomized, double-blinded (for the initial injection), placebo-controlled trial in PSAR/MCD vs Comparison adults and adolescents. Participants received a double-blinded injection with Pfizer-BioNTech or Moderna COVID-19 vaccine or placebo, followed by unblinded vaccine injections. The primary outcome was the incidence of clinically-determined systemic allergic reactions within 90 minutes after injection.</p><p><strong>Results: </strong>The trial enrolled 723 participants of a planned 3400, with 664 (56% PSAR/MCD) receiving at least one injection. Within 90 minutes of injection, systemic allergic reactions occurred in 5/180 (3%) PSAR/MCD participants given Pfizer-BioNTech (vs 0/133 [0%] Comparison Group; p=0.063) and 2/173 (1%) PSAR/MCD participants given Moderna (vs 0/144 [0%] Comparison Group; p=0.27). Reactions were also reported >90 minutes and ≤48 hours only in PSAR/MCD. Among PSAR/MCD participants, reaction rates to vaccine within 90-minutes and 48-hours were similar to placebo. Extensive laboratory studies did not identify plausible reaction mechanisms.</p><p><strong>Conclusions: </strong>Systemic allergic reactions based solely on clinical determination within 90-minutes or 48-hours of vaccination were only observed in PSAR/MCD but failure to achieve planned enrollment limited statistical precision. Reactions to placebo and failure to identify underlying immunologic mechanisms suggest non-allergic or non-immunologic causes.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181957","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":"Type I autoimmunity in chronic spontaneous urticaria: Evidence, limits, and endotype overlap.","authors":"George N Konstantinou, Clive E H Grattan","doi":"10.1016/j.jaci.2026.10.001","DOIUrl":"10.1016/j.jaci.2026.10.001","url":null,"abstract":"<p><p>Chronic spontaneous urticaria (CSU) is a mast cell-driven disorder with basophil involvement and several possible upstream mechanisms. Type IIb autoimmune CSU, mediated by functional IgG autoantibodies against FcεRIα or IgE, is the best-validated endotype. Evidence for type I autoimmune (autoallergic) CSU is less complete, but findings involving IgE autoantibodies to thyroid peroxidase (TPO), IL-24, and other self-antigens suggest that IgE-dependent autoreactivity may be relevant in some patients. However, total IgE level, atopy, allergic disease, and timing of the response to omalizumab are not diagnostic of this mechanism. Rather than viewing type I and type IIb CSU as competing categories, we hypothesize 2 potentially overlapping immunologic axes: an IgE-autoantibody axis and an IgG/complement axis. Patients may lie closer to one axis, show markers of both, or remain provisionally idiopathic because current biomarkers cannot classify them with confidence. Progress will require harmonized functional assays; skin, mast cell, and basophil readouts, as well as longitudinal treatment studies. The central question is when an IgE autoantibody is only a passenger, when it is a partner, and when it is the driver of the wheal.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182015","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 of Dupilumab for Patients with Chronic Rhinosinusitis without Nasal Polyps: a Randomized Double-Blind Placebo Controlled Phase II Study.","authors":"Jody Tversky, Andrew P Lane, John Schroeder, Joseph Ozeryanskiy, Christopher Hansen, Jean Kim, Antoine Azar, Scott Nash, Mark Corbett, Amr Radwan, Nicholas R Rowan","doi":"10.1016/j.jaci.2026.08.032","DOIUrl":"https://doi.org/10.1016/j.jaci.2026.08.032","url":null,"abstract":"<p><strong>Background: </strong>Chronic rhinosinusitis without nasal polyps (CRSsNP) is a heterogeneous inflammatory disease affecting up to 8% of the population. No biologic therapies are currently approved for CRSsNP, and emerging data suggest that T2-high endotypes may respond preferentially to targeted therapy.</p><p><strong>Objective: </strong>To evaluate the efficacy and safety of dupilumab, a monoclonal antibody targeting the interleukin-4/interleukin-13 signaling pathway, in patients with moderate-severe CRSsNP and to explore differential responses by T2-inflammatory endotype.</p><p><strong>Methods: </strong>In a 6-month, randomized, double-blind, placebo-controlled trial, 33 adults with moderate-severe CRSsNP received dupilumab 300 mg or placebo every 2 weeks. Primary outcomes were change in 22-item Sino-Nasal Outcome Test (SNOT-22) and mini-Rhinoconjunctivitis Quality of Life Questionnaire (mini-RQLQ) scores. Secondary outcomes included CT sinus scores and use of rescue medications. Prespecified subgroup analyses were performed in T2-high patients, defined by pronounced allergen skin test positivity or elevated blood eosinophils.</p><p><strong>Results: </strong>Dupilumab significantly improved SNOT-22 (-7.0 vs placebo; P<.001) and mini-RQLQ (-5.2 vs placebo; P<.01) scores. T2-high patients showed numerically greater improvement in SNOT-22 (-11.3; P=.07) and significant improvement in mini-RQLQ (-9.2; P<.01). Reductions in CT scores and rescue medication use favored dupilumab but were not statistically significant. Treatment was well tolerated, and all participants completed the study.</p><p><strong>Conclusion: </strong>Dupilumab was associated with meaningful improvements in patient-reported outcomes in adults with CRSsNP. The observed trend toward enhanced benefit in T2-high patients supports the potential for endotype-directed therapy and underscores the need for larger studies to evaluate the role of T2-targeted biologics in CRSsNP management.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149149123","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":"Integrated-omics endotyping of patients with chronic rhinosinusitis with nasal polyps and their response to glucocorticoid therapy.","authors":"Bing Yan, Chen Meng, Mi Lu, Mu Xian, Xiaomo Wang, Yuzhoujia Deng, Jing Wang, Zhen Chen, Luo Zhang, Chengshuo Wang","doi":"10.1016/j.jaci.2026.07.029","DOIUrl":"https://doi.org/10.1016/j.jaci.2026.07.029","url":null,"abstract":"<p><strong>Background: </strong>Integrated omics approaches provide deeper insights into disease heterogeneity, but combined host immune and nasal microbiota profiles in chronic rhinosinusitis with nasal polyps (CRSwNP) remain poorly characterized.</p><p><strong>Objective: </strong>This study aimed to identify biologically distinct CRSwNP endotypes by integrating transcriptomic and microbiota data from nasal brushings and to assess responses to corticosteroid therapy across these endotypes.</p><p><strong>Methods: </strong>Baseline transcriptomic and microbiota data from the multicenter COMPASS cohort (ClinicalTrials.gov registration: NCT05598424) were integrated using similarity network fusion and hierarchical clustering. Differential gene expression and bacterial genus abundance analyses were performed to characterize each endotype. In the COMPASS cohort, patients with CRSwNP who had a bilateral nasal polyp score (NPS) ≥ 4 points were enrolled and received 4 weeks of intranasal corticosteroid (INCS) treatment. Those whose NPS remained ≥4 after INCS treatment received a 2-week course of add-on systemic corticosteroid (SCS) therapy. Response rates were compared across endotypes using χ² or Fisher's exact tests.</p><p><strong>Results: </strong>Among 132 patients from 20 hospitals in China, four endotypes were identified: one non-type 2 inflammatory endotype (Cluster A) and three type 2 inflammatory endotypes distinguished by microbiota composition: a Corynebacterium-dominated profile (Cluster B), a Staphylococcus-dominated profile (Cluster C), and a polymicrobial profile (Cluster D). Among patients receiving add-on SCS therapy, Cluster C showed the highest observed response rate (94.1%), followed by Cluster D (72.7%), Cluster B (62.5%), and Cluster A (56.7%).</p><p><strong>Conclusion: </strong>Integrated transcriptome and microbiota analysis identified four CRSwNP endotypes with distinct immune-microbial signatures and variable corticosteroid responsiveness, supporting the potential for endotype-driven precision therapy in CRSwNP.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149149403","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":"Thymic stromal defects and immune dysregulation in hypomorphic Rag deficiency: implications for hematopoietic cell transplantation.","authors":"Francesca Pala, Cihan Oguz, Cristina Corsino, Ian Lamborn, Andrew J Martins, John S Tsang, Ronald N Germain, Justin Lack, Luigi D Notarangelo, Marita Bosticardo","doi":"10.1016/j.jaci.2026.09.023","DOIUrl":"https://doi.org/10.1016/j.jaci.2026.09.023","url":null,"abstract":"<p><strong>Background: </strong>Thymic epithelial cells (TEC) are essential for positive and negative selection during T-cell development. Hypomorphic RAG deficiency is characterized by T-cell lymphopenia and an increased risk of infections and autoimmunity. However, whether abnormalities of TEC composition and function also contribute to these clinical features is unknown.</p><p><strong>Objective: </strong>Using a Rag1 hypomorphic (Rag1^mut) mouse model, we examined composition and function of the TEC compartment, both before and after hematopoietic stem cell transplantation (HSCT).</p><p><strong>Methods: </strong>Flow cytometry, immunofluorescent imaging, and single cell RNA sequencing were used to characterize the TECs and thymocytes. Bone marrow transplantation studies were performed to define level of donor chimerism required to fully correct thymic abnormalities.</p><p><strong>Results: </strong>The thymus of Rag1^mut mice is small, with an increased proportion of cortical and a severe reduction of medullary TECs, and reduced expression of tissue-restricted antigens. Transplantation of Rag1^mut HSCs into wild-type mice phenocopied the altered thymic architecture of Rag1^mut mice. Transplantation of wild-type HSCs into Rag1^mut mice fully corrected thymocyte development, and normalized the TEC phenotype. However, in competitive settings, lower levels of wild-type HSC engraftment were associated with persistence of mutant-derived double-negative thymocytes and of a low number of Itgβ4⁺ mTEC^lo cells, incomplete restoration of the TEC compartment, and autoantibody production.</p><p><strong>Conclusion: </strong>Impaired thymocyte development in Rag1^mut mice leads to abnormal TEC composition and immune dysregulation, whose correction requires robust levels of donor chimerism after HSCT.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149148165","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":"Being mentored and mentoring: Expect the unexpected.","authors":"R Stokes Peebles","doi":"10.1016/j.jaci.2026.09.022","DOIUrl":"10.1016/j.jaci.2026.09.022","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136999","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 tissue-informed blood proteomic signature of eosinophilic gastritis activity.","authors":"Molly Ahye, Hironori Sato, Rebekah Karns, Yusuke Kawashima, Mark Rochman, Mari Yamaguchi, Yuichiro Tanaka, Kazuhiro Matsuyama, Sung Hwan Yoon, Aleksandra Nita-Lazar, Nirmala P Gonsalves, Marc E Rothenberg, Tetsuo Shoda","doi":"10.1016/j.jaci.2026.09.006","DOIUrl":"https://doi.org/10.1016/j.jaci.2026.09.006","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137047","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.2026.08.012","DOIUrl":"10.1016/j.jaci.2026.08.012","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"158 4","pages":"Pages 949-950"},"PeriodicalIF":11.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149095605","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":"Scientific Advances from Sharing URECA Data in Collaborative Analyses","authors":"James E. Gern,Leonard B. Bacharier,Meyer Kattan,Katherine Rivera-Spoljarik,Robert A. Wood,Carole Ober,Cynthia M. Visness,Lisa Gagalis,Alkis Togias,Patrice M. Becker,Daniel J. Jackson,William W. Busse,George T. O’Connor","doi":"10.1016/j.jaci.2026.09.020","DOIUrl":"https://doi.org/10.1016/j.jaci.2026.09.020","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"148 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149090245","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":"SERPINE1 promoter variants and differential airway responses to virus and biological therapy","authors":"Ariel Helms Thames,Madeline Schutt,Samantha Gadd,Leonardo Barrera,Seong Cho,William Wentworth-Sheilds,Jacqueline Pongracic,Andrew H. Liu,Rebecca Gruchalla,Carolyn Kercsmar,Gurjit Khurana Hershey,Edward Zoratti,Christine Johnson,Stephen Teach,Meyer Kattan,Michael Nodzenski,Courtney Gaberino,Leonard Bacharier,George T. O’Connor,James Gern,Cynthia Visness,Amaziah Coleman,Peter Gergen,Patrice Becker,Carole Ober,Daniel Jackson,Matthew Altman,Rajesh Kumar","doi":"10.1016/j.jaci.2026.08.020","DOIUrl":"https://doi.org/10.1016/j.jaci.2026.08.020","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"3 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149090247","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}