Journal of Allergy and Clinical Immunology最新文献

{"title":"Thymic stromal defects and immune dysregulation in hypomorphic recombinase activating gene (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":"10.1016/j.jaci.2026.09.023","url":null,"abstract":"<p><strong>Background: </strong>Thymic epithelial cells (TECs) are essential for positive and negative selection during T-cell development. Hypomorphic recombinase activating gene (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.</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, as well as reduced expression of tissue-restricted antigens. Transplantation of Rag1^mut hematopoietic stem cells into wild-type mice phenocopied the altered thymic architecture of Rag1^mut mice. Transplantation of wild-type hematopoietic stem cells into Rag1^mut mice fully corrected thymocyte development and normalized the TEC phenotype. However, in competitive settings, lower levels of wild-type hematopoietic stem cell engraftment were associated with persistence of mutant-derived double-negative thymocytes and of a low number of Itgβ4-positive, medullary TEC-low 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 hematopoietic stem cell transplantation.</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}

{"title":"International perspective on obtaining disease modification with food allergy therapies","authors":"Aikaterini Anagnostou MD, PhD,&nbsp;Phillipe Bégin MD,&nbsp;Thomas Eiwegger MD,&nbsp;Matthew Greenhawt MD, MBA, MSc,&nbsp;Douglas P. Mack MD,&nbsp;Alkis Togias MD","doi":"10.1016/j.jaci.2026.07.007","DOIUrl":"10.1016/j.jaci.2026.07.007","url":null,"abstract":"<div><h3>Background</h3><div>A disease-modifying therapy aims to alter natural history by delaying or reversing disease progression.</div></div><div><h3>Objective</h3><div>We examined expert opinion regarding the concept of disease modification in food allergy to assess consensus, definitions, and identification of relevant biomarkers.</div></div><div><h3>Methods</h3><div>We contextualized relevant definitions to terms such as <em>desensitization, sustained unresponsiveness, tolerance,</em> and <em>remission;</em> and evaluated evidence-based disease-modifying effects of therapeutic strategies.</div></div><div><h3>Results</h3><div>Evidence from oral, epicutaneous and sublingual immunotherapy demonstrates that desensitization is common and that a subset of patients has disease with sustained unresponsiveness or remission after treatment discontinuation. Younger age and lower baseline allergen-specific IgE may predict more durable responses. Immunologic changes associated with these outcomes include suppression of type 2 cellular responses, modulation of B-cell compartments, and induction of blocking antibodies. Currently approved biologics enhance protection during active treatment but have limited evidence for direct disease modification, although they may facilitate tolerance when combined with allergen exposure.</div></div><div><h3>Conclusions</h3><div>While the clinical states of desensitization, sustained unresponsiveness, tolerance, and remission may involve partial or complete disease modification in food allergy, no consensus definition exists, and no relevant biomarkers have been identified to date.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"158 4","pages":"Pages 1010-1017"},"PeriodicalIF":11.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148584372","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 miRNAome-transcriptome analyses identify an immuno-hematopoietic subcluster in patients with long COVID","authors":"Ying Yang PhD,&nbsp;Mari Kanerva MD, PhD,&nbsp;Helena Liira MD, PhD,&nbsp;Aki Vuokko MD, PhD,&nbsp;Sini Laakso MD, PhD,&nbsp;Velina Vangelova-Korpinen MD,&nbsp;Shuyuan Wang PhD,&nbsp;Kirsi Kvarnström PhD,&nbsp;Mikko Varonen PhD,&nbsp;Hille Suojalehto MD, PhD,&nbsp;Antti Lauerma MD, PhD,&nbsp;Piia Karisola PhD,&nbsp;Harri Alenius PhD","doi":"10.1016/j.jaci.2026.05.032","DOIUrl":"10.1016/j.jaci.2026.05.032","url":null,"abstract":"<div><h3>Background</h3><div>Persistent symptoms following SARS-CoV-2 infection, termed post-COVID-19 condition or long COVID (LC), impose substantial psychological and socioeconomic burdens. However, microRNA (miRNA)-mRNA interactions underlying LC heterogeneity remain incompletely defined.</div></div><div><h3>Objective</h3><div>We sought to determine whether integrative blood miRNA-mRNA profiling identifies molecular LC subclusters linked to clinical and immuno-hematopoietic features.</div></div><div><h3>Methods</h3><div>We performed integrated miRNAome-transcriptome profiling of circulating blood RNA from individuals with LC and recovered control participants. Differential miRNA and mRNA expression was assessed using limma software, and hierarchical clustering was used to define LC subclusters. Validated miRNA-mRNA interaction networks were constructed using the miRNet tool. Clinical, functional, and biochemical parameters were compared between subclusters, and a random forest classifier was developed.</div></div><div><h3>Results</h3><div>Clustering identified an immuno-hematopoietic LC subcluster, LC1, characterized by extensive miRNA-mRNA dysregulation; enrichment of erythropoietic, platelet, and immune pathways; and biochemical alterations including lower plasma sodium and elevated fibrin D-dimer and thrombin time. Compared with subcluster LC2, LC1 showed persistently greater symptom burden, functional impairment, reduced quality of life, lower resilience, and higher anxiety/depressive symptoms. Potential confounding by age, sex, comorbidities, and selected medication use was evaluated. Network and coexpression analyses identified regulatory nodes enriched for viral infection and natural killer cell activation pathways. A random forest classifier incorporating 9 miRNAs and <em>LRRFIP2</em> achieved an area under the receiver operating characteristic curve of 0.91 for LC1, distinguishing LC1 from LC2 and recovered control participants.</div></div><div><h3>Conclusions</h3><div>LC comprises biologically and clinically distinct subclusters shaped by coordinated miRNA-mRNA remodeling. The immuno-hematopoietic LC1 subcluster supports biomarker-based stratification of patients with persistent physiologic and clinical impairment.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"158 4","pages":"Pages 1133-1148.e13"},"PeriodicalIF":11.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148305016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antigen-specific messenger RNA lipid nanoparticle therapy with mTOR inhibition promotes regulatory T cells and limits allergy","authors":"Yrina Rochman PhD,&nbsp;Jilian R. Melamed PhD,&nbsp;Andrea M. Klingler MS,&nbsp;Michael Kotliar ME,&nbsp;Mark Rochman PhD,&nbsp;Julie M. Caldwell PhD,&nbsp;Jennifer M. Felton PhD,&nbsp;Garrett A. Osswald BS,&nbsp;Jenna Muscat-Rivera BS,&nbsp;Michael Kegel BSE,&nbsp;Artem Barski PhD,&nbsp;Ian P. Lewkowich PhD,&nbsp;Drew Weissman MD, PhD,&nbsp;Marc E. Rothenberg MD, PhD","doi":"10.1016/j.jaci.2026.05.023","DOIUrl":"10.1016/j.jaci.2026.05.023","url":null,"abstract":"<div><h3>Background</h3><div>Immune tolerance in allergic diseases is associated with attenuation of T_H2 responses by shifting of antigen-specific immunity toward T_H1 and regulatory T-cell pathways, but current strategies incompletely induce durable regulatory immunity.</div></div><div><h3>Objective</h3><div>We determined whether combining an allergen-encoded messenger RNA (mRNA) lipid nanoparticle (LNP) vaccine with inhibition of the mechanistic target of rapamycin (mTOR) enhances regulatory T-cell responses.</div></div><div><h3>Methods</h3><div>Mice were immunized with an allergen-encoded mRNA-LNP vaccine alone or in combination with an mTOR inhibitor, followed by induction of a preclinical model of allergic asthma. Antigen-specific T-cell responses, eosinophil activation, airway hyperresponsiveness, mucus production, and markers of cytotoxicity were assessed.</div></div><div><h3>Results</h3><div>Immunization with allergen-encoded mRNA-LNP elicited T_H1-associated and cytotoxic CD8⁺ T responses that counterbalanced T_H2 immunity. Coadministration with an mTOR inhibitor shifted this profile by promoting generation of functional regulatory T cells and attenuating IFN-γ production and CD8⁺ T-cell responses. This combinatorial strategy preserved the antiallergic effects of mRNA-LNP immunization, reduced eosinophil activation markers, and limited vaccine-associated cytotoxicity.</div></div><div><h3>Conclusion</h3><div>The ability of an mTOR inhibitor to profoundly modify mRNA-LNP therapy by inducing regulatory T cells presents a potential strategy to enhance regulatory immunity in the treatment of allergy and other inflammatory diseases.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"158 4","pages":"Pages 1058-1072"},"PeriodicalIF":11.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148211287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative efficacy of biologic agents for severe chronic rhinosinusitis with nasal polyps: Systematic review and network meta-analysis","authors":"Konstantinos Ouranos MD,&nbsp;Mark Michael MD,&nbsp;Evangelia K. Mylona MSc,&nbsp;Sophia C. Mylonakis MSc,&nbsp;Akash Guruswamy MD,&nbsp;Fadi Shehadeh MSc,&nbsp;Tina Motazedi MD,&nbsp;David P. Huston MD","doi":"10.1016/j.jaci.2026.06.016","DOIUrl":"10.1016/j.jaci.2026.06.016","url":null,"abstract":"<div><h3>Background</h3><div>Biologic therapies improve outcomes in severe chronic rhinosinusitis with nasal polyps (CRSwNP), but their comparative efficacy remains uncertain.</div></div><div><h3>Objective</h3><div>We compared the efficacy and safety of 7 biologic agents (dupilumab, omalizumab, mepolizumab, benralizumab, depemokimab, tezepelumab, and stapokibart) for the treatment of severe CRSwNP.</div></div><div><h3>Methods</h3><div>We systematically reviewed randomized trials in PubMed and EMBASE evaluating biologic agents for severe CRSwNP. Primary outcomes were changes in nasal polyp score (NPS) and nasal congestion score (NCS) at 20-24 and 48-56 weeks. Secondary outcomes included changes in loss-of-smell test, 22-item Sinonasal Outcome Test, University of Pennsylvania Smell Identification Test, Lund-Mackay scores, need for nasal polyp surgery or systemic corticosteroids, and safety. We used mean differences and odds ratios with 95% confidence intervals for analysis.</div></div><div><h3>Results</h3><div>Fifteen randomized trials involving 3,642 patients were included. At 20-24 weeks, dupilumab and stapokibart produced greater reductions in NPS and NCS compared to depemokimab, omalizumab, and benralizumab, with no significant differences between dupilumab and stapokibart for NPS (mean difference [95% confidence interval]: 0.29 [−0.97, 0.40]) and NCS (0.19 [−0.03, 0.42]). At 48-56 weeks, dupilumab and tezepelumab produced greater reductions in NPS and NCS than depemokimab, mepolizumab, or benralizumab; no significant differences were observed between dupilumab and tezepelumab for NPS (0.32 [−0.17, 0.81]) and NCS (0.06 [−0.19, 0.31]). Dupilumab, tezepelumab (at 48-56 weeks only), and stapokibart (at 20-24 weeks only) showed superior outcomes for secondary end points against other tested biologics. Safety profiles were comparable across agents.</div></div><div><h3>Conclusion</h3><div>Dupilumab, tezepelumab, and stapokibart were associated with greater clinical benefit than other biologics in severe CRSwNP. Indirect comparisons did not demonstrate superiority of stapokibart (at 20-24 weeks) or tezepelumab (at 48-56 weeks) over dupilumab, highlighting the need for direct comparative trials.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"158 4","pages":"Pages 1047-1057"},"PeriodicalIF":11.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148379753","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}