Journal of Allergy and Clinical Immunology最新文献

{"title":"Comparative efficacy and safety of biologics and systemic immunomodulatory treatments for chronic urticaria: Systematic review and network meta-analysis","authors":"Alexandro W.L. Chu MD ,&nbsp;Paul Oykhman MD ,&nbsp;Xiajing Chu MPH ,&nbsp;Daniel G. Rayner MSc ,&nbsp;Sukhdeep Bhangal MD ,&nbsp;Andrew Dam BHSc ,&nbsp;Janice Xu BHSc ,&nbsp;Javed Sheikh MD ,&nbsp;Kathryn P. Trayes MD ,&nbsp;Winfred T. Frazier MPH ,&nbsp;David M. Lang MD ,&nbsp;Lisa A. Beck MD ,&nbsp;Sameer K. Mathur PhD ,&nbsp;Susan Waserman MD ,&nbsp;Lehana Thabane PhD ,&nbsp;Rachel N. Asiniwasis MD ,&nbsp;Lauren Runyon MSN ,&nbsp;Joseph Moellman MD ,&nbsp;Eric T. Oliver MD ,&nbsp;Jeffrey Chan MD ,&nbsp;Derek K. Chu MD, PhD","doi":"10.1016/j.jaci.2025.06.004","DOIUrl":"10.1016/j.jaci.2025.06.004","url":null,"abstract":"<div><h3>Background</h3><div>Chronic urticaria is a common skin condition characterized by itchy wheals (hives), angioedema, or both, lasting for 6 weeks or more. Beyond antihistamines, multiple systemic treatments are available, but there is uncertainty regarding their comparative effects on chronic urticaria outcomes.</div></div><div><h3>Objective</h3><div>We systematically synthesized the comparative benefits and harms of systemic treatments for chronic urticaria.</div></div><div><h3>Methods</h3><div>As part of updating the AAAAI/ACAAI JTFPP chronic urticaria guidelines, we searched Medline, Embase, Central, Chinese Biomedical Databases (CBM), China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), and Wanfang from inception to February 4, 2025, for randomized trials addressing systemic immunomodulatory treatments, including phototherapy, for chronic urticaria. Paired reviewers screened records, extracted data, and assessed risk of bias. Random effects Bayesian network meta-analyses addressed urticaria activity (comprising itch and wheal scores), angioedema activity, health-related quality of life, and adverse events. The GRADE approach informed certainty-of-evidence ratings (PROSPERO: CRD42023429819).</div></div><div><h3>Results</h3><div>We included 93 studies (n = 11,398; mostly adult and adolescent participants across 83 randomized trials and 10 nonrandomized studies) that evaluated 42 interventions. With high certainty, standard-dose omalizumab (300 mg every 4 weeks) and remibrutinib are among the most effective for improving multiple patient-important outcomes. The safety profile of remibrutinib, however, is less certain. Dupilumab improved urticaria activity, but its impact on quality of life is uncertain, and no dupilumab trials addressed angioedema activity. Cyclosporine may be among the most effective for improving urticaria activity but may be among the most harmful in increasing the frequency of any adverse events. Azathioprine, dapsone, hydroxychloroquine, mycophenolate, sulfasalazine, and vitamin D may improve outcomes, while benralizumab, quilizumab, and tezepelumab may not differ from placebo, though the evidence is uncertain. Findings were consistent across age groups and baseline severity, and were robust to subgroup analyses.</div></div><div><h3>Conclusions</h3><div>Among individuals with chronic urticaria refractory to antihistamines, standard-dose omalizumab and remibrutinib are among the most effective drugs across multiple patient-important outcomes with a favorable safety profile across the studied duration. Cyclosporine may be effective but may be among the most harmful. Dupilumab improves itch and wheals, but it is uncertain whether it improves angioedema or quality of life. Lower doses of omalizumab are of intermediate effectiveness and favorable safety. The net benefit of conventional immunosuppressants is uncertain.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"156 4","pages":"Pages 1008-1023"},"PeriodicalIF":11.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144630434","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":"Corrigenda","authors":"","doi":"10.1016/j.jaci.2025.07.022","DOIUrl":"10.1016/j.jaci.2025.07.022","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"156 4","pages":"Page 1124"},"PeriodicalIF":11.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144821494","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":"Beyond conventional adoptive T-cell therapy","authors":"Marina Cavazzana MD, PhD ,&nbsp;Juliette Paillet PhD ,&nbsp;Abderrahim Fandi MD, PhD ,&nbsp;Ranjita Devi Moirangthem PhD ,&nbsp;Pierre Heimendinger PhD ,&nbsp;Elisa Magrin PharmD, PhD ,&nbsp;Sebastien Oster PharmD ,&nbsp;Saulius Zuklys PhD ,&nbsp;Raynier Devillier MD ,&nbsp;Anne Huynh MD ,&nbsp;Simona Piemontese PhD ,&nbsp;Fabio Ciceri MD ,&nbsp;Elena Tassi MD, PhD ,&nbsp;Maddalena Noviello MD ,&nbsp;Chiara Bonini MD, PhD ,&nbsp;Georg Holländer ,&nbsp;Eliane Gluckman MD, PhD ,&nbsp;Tayebeh-Shabi Soheili PhD ,&nbsp;Aurelie Bauquet PhD ,&nbsp;Olivier Negre PhD","doi":"10.1016/j.jaci.2025.08.004","DOIUrl":"10.1016/j.jaci.2025.08.004","url":null,"abstract":"<div><div>Reconstitution of the T-cell compartment is essential in the treatment of several immune disorders. Similarly, individuals with hematologic malignancies who are undergoing allogeneic hematopoietic stem cell transplantation experience prolonged T-cell deficiencies, which increase their risk of infections and relapses. Various strategies for addressing T-cell deficiencies are based on adoptive T-cell therapies. However, challenges related to specificity, safety, scalability, and manufacturing have yet to be overcome. Human T lymphoid progenitor–based immunotherapy might be a valuable, complementary approach for increasing the effectiveness of current treatments for T-cell deficiencies. We have developed a feeder-free culture system that leverages a human DLL4-Fc fusion protein (Notch ligand) to generate human T lymphoid progenitors from CD34⁺ hematopoietic stem and progenitor cells within 7 days. The cell product, called ProTcell, is composed mainly of cells expressing CD7, chemokine receptor proteins (eg, CCR9), and adhesion molecules (eg, L-selectin). After injection in NSG mice, ProTcell can differentiate and be educated in the thymus to generate simple positive T cells. Here, we summarize the current state of preclinical and clinical research using this approach, highlighting its potential advantages and current limitations for immune reconstitution therapies.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"156 4","pages":"Pages 867-877"},"PeriodicalIF":11.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144955159","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":"Vijaya Knight, Lusia Sepiashvili","doi":"10.1016/j.jaci.2025.08.024","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.08.024","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.2,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185088","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":"BTK modulates systemic immune activation to bacterial translocation in primary antibody deficiencies.","authors":"Hsi-En Ho,Lin Radigan,Jingjing Qi,Vladimir Roudko,Michael J Storek,Jo Hsuan Lee,Ramsay Fuleihan,Kathleen Sullivan,Seunghee Kim-Schulze,Charlotte Cunningham-Rundles","doi":"10.1016/j.jaci.2025.09.019","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.09.019","url":null,"abstract":"BACKGROUNDBacterial translocation is a shared phenomenon in common variable immunodeficiency (CVID) and x-linked agammaglobulinemia (XLA). In CVID, bacterial translocation is linked to systemic immune activation and chronic inflammatory manifestations.OBJECTIVETo investigate whether the absence of functional Bruton's tyrosine kinase (BTK) in XLA is associated with protection against systemic inflammation driven by bacterial translocation, and to assess whether BTK inhibition could modulate these inflammatory responses in CVID.METHODSClinical data from the US national registry were analyzed to compare the incidence of inflammatory complications between CVID and XLA. Serum immune profiling was conducted to assess systemic immune activation associated with bacterial translocation in both disorders. In parallel, ex vivo stimulation assays were used to evaluate the effects of BTK inhibition on microbial-translocation-driven inflammatory responses in CVID.RESULTSXLA patients, who lack BTK, were significantly protected from the inflammatory complications commonly observed in CVID. Despite comparable levels of bacterial translocation, serum cytokine profiling revealed that XLA patients exhibited markedly reduced immune activation, with lower levels of IFN-γ pathway mediators (IFN-γ, IL-12b, IL-18, CXCL9), pro-inflammatory cytokines (TNF-α, TNF-β, IL-6), chemokines related to host-commensal junctures (CCL19, CCL23, CCL3), and markers of monocyte and T cell activation. XLA and CVID exhibited differential host responses to bacterial translocation stimuli in vivo and ex vivo, with reduced IFN-ɣ, pro-inflammatory cytokines, and monocyte responses in XLA. Translating these findings, we showed that the use of BTK inhibitors (rilzabrutinib, PCI-29732) in inflammatory CVID PBMCs recapitulated the in vivo differences between CVID and XLA, and effectively attenuated pathogenic immune responses to bacterial translocation stimuli.CONCLUSIONSThese findings identify BTK as a key host modifier mediating the systemic effects of bacterial translocation. Inhibiting BTK activity in CVID may provide a novel therapeutic strategy to mitigate chronic inflammatory complications in this primary antibody deficiency.","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"29 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145203881","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":"Cytokine testing: Asking the right questions.","authors":"Paul M Gallo","doi":"10.1016/j.jaci.2025.08.023","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.08.023","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"326 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182730","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":"Decreased anaphylaxis by probiotic E. coli overexpressing Siglec ligand and peanut allergen.","authors":"Juan M Zilic,Timothey G Keys,Thierry Hennet","doi":"10.1016/j.jaci.2025.09.022","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.09.022","url":null,"abstract":"BACKGROUNDOral immunotherapies for food allergies remain limited by safety concerns and inconsistent efficacy.OBJECTIVEWe developed a probiotic-based strategy using Escherichia coli Nissle 1917 (EcN) engineered to co-display the major peanut allergen Ara h 2 and the inhibitory Siglec ligand Sia(α2-6)Gal(β1-4)Glc to dampen allergen-specific B cell responses.METHODSExpression of Siglec ligand and Ara h 2 on EcN was confirmed by Western blot and flow cytometry. C3H/HeJ mice were sensitized by intraperitoneal injections and treated orally with bacteria. B cell responses were assessed by flow cytometry after in vitro stimulation of splenocytes. Serum antibody and mast cell protease levels were measured by ELISA. Anaphylaxis protection was evaluated through hypothermia and symptom scores.RESULTSIn vitro stimulation with peanut extract increased B cell activation in sensitized splenocytes, and wild-type EcN further enhanced this activation. In contrast, EcN displaying Ara h 2 and Siglec ligands significantly reduced CD23 upregulation and restored CD86 and CD69 expression. Oral administration of EcN displaying Ara h 2 and Siglec ligands to peanut-sensitized mice reduced allergen-specific B cell activation, decreased serum IgE and IgG levels, and significantly attenuated anaphylactic responses. EcN co-displaying Ara h 2 and Siglec ligand conferred protection, highlighting the requirement for antigen-specific engagement of inhibitory B cell pathways. While this study focused on Ara h 2, including multiple allergens could extend protection.CONCLUSIONOur findings establish proof-of-concept for orally delivered antigen-specific immune tolerance using engineered probiotics, providing a scalable, non-invasive alternative to intravenous nanoparticle therapies. This approach could be extended to other allergies or autoimmune conditions.","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"101 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145203459","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":"Explaining divergent food allergy phenotypes through failures in T- and B-cell tolerance.","authors":"David A Hill","doi":"10.1016/j.jaci.2025.09.015","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.09.015","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"13 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182733","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":"Late Effects After Haematopoietic Stem Cell Transplantation in patients with HLH: A Histiocyte Society, PDWP, IEWP and TCWP EBMT Study.","authors":"Ramme K,Horne Ac,Beutel K,Galimard Je,Alahmari A,Ottaviano G,Moshous D,Kansoy S,Nademi Z,Faraci M,Sundin M,Fagioli F,Albert Mh,Sedlacek P,Bertrand Y,Locatelli F,Paillard C,Mellgren K,Müller I,Greil J,Balduzzi A,Slatter M,Dalissier A,Kalwak K,Lankester A,Neven B,Baker Ks,Rao K,Corbacioglu S","doi":"10.1016/j.jaci.2025.09.014","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.09.014","url":null,"abstract":"BACKGROUNDHematopoietic stem cell transplantation is the only curative treatment in primary hemophagocytic lymphohistiocytosis. However, hematopoietic stem cell transplantation is associated with a wide range of late effects.OBJECTIVECharacterization of the long-term outcome and late effects following hematopoietic stem cell transplantation in primary hemophagocytic lymphohistiocytosis.METHODS274 children with pHLH from the EBMT registry who underwent allogeneic hematopoietic stem cell transplantation between 2004 and 2015 were included. Multivariable logistic regression models were performed to evaluate the adjusted impact of baseline variables on CNS and hormonal late effects, respectively.RESULTSA broad spectrum of late effects was identified, with neurological (31%) and hormonal (34.8%) complications being the most prevalent. Chemotherapy (HLH-94/HLH04) before hematopoietic stem cell transplantation was identified as a significant risk factor for endocrinological late effects (p=0.03), highlighting a novel aspect not previously reported. The presence of neurological abnormality at diagnosis was an independent risk factor for neurological late effects (p<0.001) as was incomplete remission status at time of HCT (p=0.04).CONCLUSIONHematopoietic stem cell transplantation has significantly improved survival in primary hemophagocytic lymphohistiocytosis patients, however survivors still face significant risks of late effects.","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"3 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182732","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":"Allergen Chip Challenge: a nationwide open database supporting allergy prediction algorithms.","authors":"Guillaume Martinroche,Amir Guemari,Pol André Apoil,Isabella Annesi-Maesano,Eric Fromentin,Laurent Guilleminault,Davide Caimmi,Caroline Klingebiel,Céline Beauvillain,Alain Didier,Jeremy Corriger,Pascal Demoly,Joana Vitte,Julien Goret","doi":"10.1016/j.jaci.2025.09.017","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.09.017","url":null,"abstract":"BACKGROUNDAllergen chip technologies are a powerful tool for simultaneous analysis of hundreds of allergens, generating a comprehensive sensitization landscape for precision medicine in allergy. This considerable amount of data requires extensive knowledge for translation into clinically relevant conclusion.OBJECTIVETo harness Machine Learning (ML) for allergen chip interpretation in daily practice, we set out to establish a nationwide, open database of allergen chip, demographic and clinical information and to submit it to an international crowdsourced ML competition to generate a predictive allergy classification algorithm.METHODSThe project consortium defined 20 clinical variables and 5 demographic factors for retrospective collection in conjunction with allergen chip IgE data (2014-2023) from 11 French University Hospitals. The dataset was processed to tag confirmed allergy, grade of severity, and culprit allergen identification associated with allergen chip data and submitted to the data challenge.RESULTSData were collected for 4,271 patients, yielding a dataset with over 700,000 specific IgE data points. Sensitization was present in 3579 patients (84%). Allergy was confirmed in 2,236 patients (53%) and excluded in 1,076 patients, the remaining 959 being missing outcome data (allergy diagnosis labels). The competition attracted 292 data scientists who submitted 3,135 algorithms. The highest F-scores ranged from 0.780 to 0.786. The database was subsequently made available as an open source.CONCLUSIONSWe present a nationwide open allergy database designed to enable the development of predictive algorithms. This scalable framework, integrating clinical data with ML techniques paves the way for data-driven allergen chip use and interpretation by allergists.","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"28 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182647","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}