Journal of Allergy and Clinical Immunology最新文献

{"title":"Phase 2b randomized clinical trial of amlitelimab, an anti-OX40 ligand antibody, in patients with moderate-to-severe atopic dermatitis","authors":"Stephan Weidinger MD, PhD ,&nbsp;Andrew Blauvelt MD, MBA ,&nbsp;Kim A. Papp MD, PhD ,&nbsp;Adam Reich MD, PhD ,&nbsp;Chih-Hung Lee MD, PhD ,&nbsp;Margitta Worm MD ,&nbsp;Charles Lynde MD ,&nbsp;Yoko Kataoka MD ,&nbsp;Peter Foley MD ,&nbsp;Xiaodan Wei PhD ,&nbsp;Wanling Wong PhD ,&nbsp;Anne-Catherine Solente MSc ,&nbsp;Christine Weber MD ,&nbsp;Samuel Adelman MD ,&nbsp;Sonya Davey MD ,&nbsp;Fabrice Hurbin PharmD ,&nbsp;Natalie Rynkiewicz PhD ,&nbsp;Karl Yen MD ,&nbsp;John T. O’Malley MD, PhD ,&nbsp;Charlotte Bernigaud MD, PhD","doi":"10.1016/j.jaci.2024.10.031","DOIUrl":"10.1016/j.jaci.2024.10.031","url":null,"abstract":"<div><h3>Background</h3><div>Amlitelimab, a fully human nondepleting mAb targeting OX40 ligand on antigen-presenting cells, could prevent T-cell–driven inflammation seen in atopic dermatitis (AD).</div></div><div><h3>Objective</h3><div>This trial evaluated the efficacy and safety of amlitelimab in adults with AD.</div></div><div><h3>Methods</h3><div>In this 2-part, phase 2b, randomized, double-blinded placebo-controlled trial (<span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> identifier NCT05131477), patients received subcutaneous amlitelimab every 4 weeks at doses of 250 mg plus a 500-mg loading dose, 250 mg, 125 mg, or 62.5 mg or placebo for 24 weeks in Part 1 (1:1:1:1:1 randomization). In Part 2, clinical responders were reallocated 3:1 to stop taking amlitelimab or continue the previous dose regimen for 28 weeks. The primary end point was percentage of change in Eczema Area and Severity Index (EASI) from baseline to week 16.</div></div><div><h3>Results</h3><div>In all, 390 and 190 patients enrolled in Part 1 and Part 2, respectively. A significant percentage of change decrease in EASI was observed with amlitelimab doses versus with placebo (<em>P</em> &lt; .001). Clinical responses at week 24 (Investigator Global Assessment 0/1 and/or a 75% reduction in EASI) were maintained at week 52 in patients continuing or stopping amlitelimab. Of the patients maintaining clinical response at week 52 after no longer receiving treatment, more than 80% had serum amlitelimab concentrations less than the 4-μg/mL threshold for several weeks before week 52. Reductions in AD-related biomarkers during Part 1 were maintained through Part 2. Amlitelimab was well tolerated over 52 weeks.</div></div><div><h3>Conclusions</h3><div>Amlitelimab treatment significantly reduced clinical and biomarker responses, and was well tolerated in adults with AD through week 52. Sustained responses were observed in the majority of patients for 28 weeks after they had stopped taking amlitelimab.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 4","pages":"Pages 1264-1275"},"PeriodicalIF":11.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620988","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":"Consensus of the Italian Primary Immunodeficiency Network on the use and interpretation of genetic testing for diagnosing inborn errors of immunity","authors":"Giuliana Giardino MD, PhD ,&nbsp;Gigliola Di Matteo PhD ,&nbsp;Silvia Giliani PhD ,&nbsp;Simona Ferrari PhD ,&nbsp;Vassilios Lougaris MD, PhD ,&nbsp;Raffaele Badolato MD, PhD ,&nbsp;Francesca Conti MD, PhD ,&nbsp;Roberta Romano MD, PhD ,&nbsp;Maria Pia Cicalese MD, PhD ,&nbsp;Silvia Ricci MD ,&nbsp;Federica Barzaghi MD, PhD ,&nbsp;Antonio Marzollo MD, PhD ,&nbsp;Cristina Cifaldi PhD ,&nbsp;Davide Montin MD, PhD ,&nbsp;Lorenzo Lodi MD ,&nbsp;Emilia Cirillo MD, PhD ,&nbsp;Baldassarre Martire MD ,&nbsp;Antonio Trizzino MD ,&nbsp;Mayla Sgrulletti MD ,&nbsp;Viviana Moschese MD, PhD ,&nbsp;Claudio Pignata MD, PhD","doi":"10.1016/j.jaci.2024.11.030","DOIUrl":"10.1016/j.jaci.2024.11.030","url":null,"abstract":"<div><h3>Background</h3><div>Inborn errors of immunity (IEIs) comprise more than 500 different rare congenital disorders of the immune system and are characterized by susceptibility to infection and immune dysregulation. The significant overlap of the clinical features among the different forms may lead to diagnostic delay. High-throughput sequencing techniques may allow a timely genetic definition. Guidelines for the use and the interpretation of genetic testing produced by the American College of Medical Genetics and Genomics (ACMG) and the European Society of Human Genetics (ESHG) do not cover specifics for their application to IEIs.</div></div><div><h3>Objective</h3><div>The aim of this consensus study was to define the best approach to genetic testing for IEIs.</div></div><div><h3>Methods</h3><div>A panel of experts in the context of the Italian Primary Immunodeficiency Network (IPINet) composed a list of statements that were evaluated by the Delphi method.</div></div><div><h3>Results</h3><div>The experts recommend that genetic testing for IEIs should be offered to selected patients with warning signs for IEIs and highlight the crucial role of thorough phenotyping and functional tests for the conclusive diagnosis of IEI. Comprehensive educational programs targeted to health care professionals and the public should be developed to increase IEIs awareness and reduce diagnostic delay. Ethical issues should be pondered over the diagnostic advantages of genetic tests requested for diagnostic purposes.</div></div><div><h3>Conclusion</h3><div>Adherence to guidelines on the use and interpretation of genetic tests for diagnosing IEIs should help limit the inappropriate use of these techniques, thereby reducing the risk of misdiagnosis and patient apprehension regarding inconclusive genetic results.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 4","pages":"Pages 1149-1160"},"PeriodicalIF":11.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769157","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":"Coronavirus disease 2019 (COVID-19) in children: Evolving epidemiology, immunology, symptoms, diagnostics, treatment, post–COVID-19 conditions, prevention strategies, and future directions","authors":"Juliane Wurm MD ,&nbsp;Nicole Ritz MD, PhD ,&nbsp;Petra Zimmermann MD, PhD","doi":"10.1016/j.jaci.2024.11.012","DOIUrl":"10.1016/j.jaci.2024.11.012","url":null,"abstract":"<div><div>The epidemiology of coronavirus disease 2019 (COVID-19) in children has evolved throughout the pandemic, with initially low infection rates rising significantly as a result of the emergence of the more transmissible Omicron variant. Adolescents, children from ethnic minorities and lower-income households, and those with obesity are at increased risk of contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The immune response in children leads to milder symptoms compared to adults, with fever and cough being most frequent; tough symptoms vary by SARS-CoV-2 variant and age. Diagnostic methods to confirm current or past infection include reverse transcription PCR, rapid antigen tests, and serology. Treatment is mainly supportive, with antivirals and glucocorticoids reserved for severe cases. While serious conditions like multisystem inflammatory syndrome in children and other post–COVID-19 conditions are rare, they require careful management. Vaccination has proven effective in reducing severe disease and protecting against post–COVID-19 conditions. Continued surveillance, including wastewater monitoring and universal or pooled testing, remains crucial for controlling community spread. Key questions remain regarding the duration and quality of immunity after reinfection or vaccination, the impact of coinfections, and optimal treatment protocols for different pediatric populations.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 4","pages":"Pages 1071-1081"},"PeriodicalIF":11.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647297","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":"A molecular basis for milk allergen immune recognition in eosinophilic esophagitis","authors":"Julianna Dilollo BA ,&nbsp;Alex Hu PhD ,&nbsp;Huiqi Qu MD, PhD ,&nbsp;Karina E. Canziani PhD ,&nbsp;Rachel L. Clement BS ,&nbsp;Sam J. McCright PhD ,&nbsp;Wayne G. Shreffler MD, PhD ,&nbsp;Hakon Hakonarson MD, PhD ,&nbsp;Jonathan M. Spergel MD, PhD ,&nbsp;Karen Cerosaletti PhD ,&nbsp;David A. Hill MD, PhD","doi":"10.1016/j.jaci.2025.01.008","DOIUrl":"10.1016/j.jaci.2025.01.008","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 4","pages":"Pages 1396-1399"},"PeriodicalIF":11.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074478","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":"Targeting the OX40-OX40L pathway: A new era in atopic dermatitis management by T-cell rebalancing","authors":"Saeko Nakajima MD, PhD ,&nbsp;Satoru Yonekura MD, PhD ,&nbsp;Kenji Kabashima MD, PhD","doi":"10.1016/j.jaci.2025.02.007","DOIUrl":"10.1016/j.jaci.2025.02.007","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 4","pages":"Pages 1211-1213"},"PeriodicalIF":11.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468212","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":"Autoimmunity in long COVID","authors":"Shubha Talwar MRes,&nbsp;James A. Harker PhD,&nbsp;Peter J.M. Openshaw MD, PhD,&nbsp;Ryan S. Thwaites PhD","doi":"10.1016/j.jaci.2025.02.005","DOIUrl":"10.1016/j.jaci.2025.02.005","url":null,"abstract":"<div><div>Long COVID (also termed postacute sequelae of SARS-CoV-2, or PASC) affects up to 10% of people recovering from infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Diagnosis is hampered by diffuse symptomatology, lack of biomarkers, incomplete understanding of pathogenesis, and lack of validated treatments. In terms of pathogenesis, hypothesized causes include virus persistence, the legacy of endotheliitis and thrombosis, low-grade tissue-based inflammation and/or scarring, perturbation of the host virome/microbiome, or triggering of autoimmunity. Several studies show preexisting and/or <em>de novo</em> production of autoantibodies after infection with SARS-CoV-2, but the persistence of these antibodies and their role in causing long COVID is debated. Here, we review the mechanisms through which autoimmune responses can arise during and after viral infection, focusing on the evidence for B-cell dysregulation and autoantibody production in acute and long COVID.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 4","pages":"Pages 1082-1094"},"PeriodicalIF":11.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433027","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":"Brief Overview of This Month's JACI","authors":"","doi":"10.1016/S0091-6749(25)00224-6","DOIUrl":"10.1016/S0091-6749(25)00224-6","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 4","pages":"Pages A1-A2"},"PeriodicalIF":11.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143760672","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":"Rapid validation of NLRP3 gain-of-function variants in cryopyrin-associated periodic syndromes","authors":"Alex Quach BLabMed (Hons), PhD ,&nbsp;Yunyu Lao MBiotech (Biomed) ,&nbsp;Alexander Troelnikov MBBS, BMedSci (Hons), FRACP, FRCPA ,&nbsp;Pravin Hissaria MBBS, MD, DM, FRACP, FRCPA ,&nbsp;Damien Chan MBBS, DCH, FRACP ,&nbsp;Amanda Wells BLabMedSci, MDiagGenomics, MHGSA ,&nbsp;Abhijit Kulkarni MBBS, MD ,&nbsp;Lesley Rawlings BSc(Hons), PhD ,&nbsp;Nicola Poplawski MBChB, DipPaed, FRACP, MD ,&nbsp;Antonio Ferrante PhD, FRCPath, FFSc (RCPA)","doi":"10.1016/j.jaci.2025.01.007","DOIUrl":"10.1016/j.jaci.2025.01.007","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 4","pages":"Pages 1392-1395"},"PeriodicalIF":11.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074491","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":"Targeting alarmins in asthma: From bench to clinic","authors":"Ayobami Akenroye MBChB, MPH, PhD ,&nbsp;Joshua A. Boyce MD ,&nbsp;Hirohito Kita MD","doi":"10.1016/j.jaci.2025.01.017","DOIUrl":"10.1016/j.jaci.2025.01.017","url":null,"abstract":"<div><div>Over the past 2 decades, mechanistic studies of allergic and type 2 (T2)-mediated airway inflammation have led to multiple approved therapies for the treatment of moderate-to-severe asthma. The approval and availability of these monoclonal antibodies targeting IgE, a T2 cytokine (IL-5) and/or cytokine receptors (IL-5Rα, IL-4Rα) has been central to the progresses made in the management of moderate-to-severe asthma over this period. However, there are persistent gaps in clinician’s ability to provide precise care, given that many patients with T2-high asthma do not respond to IgE- or T2 cytokine–targeting therapies and that patients with T2-low asthma have few therapeutic options. The new frontier of precision medicine in asthma, as well as in other allergic diseases, includes the targeting of epithelium-derived cytokines known as alarmins, including thymic stromal lymphopoietin, IL-25, IL-33, and their receptors. The effects of these alarmins, which can act upstream of immune cells, involve both the innate and adaptive systems and hold potential for the treatment of both T2-high and -low disease. Tezepelumab, an anti–thymic stromal lymphopoietin antibody, has already been approved for the treatment of severe asthma. In this review, we discuss our current understanding of alarmin biology with a primary focus on allergic airway diseases. We link the mechanistic corollaries to the clinical implications and advances in drug development targeting alarmins, with a particular focus on currently approved treatments, those under study, and future potential targets in alarmin signaling pathways.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 4","pages":"Pages 1133-1148"},"PeriodicalIF":11.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038986","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":"Eosinophil extracellular traps drive T follicular helper cell differentiation via VIRMA-dependent MAF stabilization in bullous pemphigoid","authors":"Shengxian Shen MD,&nbsp;Hui Fang MD,&nbsp;Xia Li MS,&nbsp;Yifan Zhou MD,&nbsp;Xin Tang MD,&nbsp;Haijun Miao MM,&nbsp;Liang Li MM,&nbsp;Jiaoling Chen PhD,&nbsp;Ke Xue PhD,&nbsp;Chen Zhang MD,&nbsp;Mengyang Chu MM,&nbsp;Bingyu Pang MM,&nbsp;Yaxing Bai MM,&nbsp;Hongjiang Qiao MD,&nbsp;Erle Dang PhD,&nbsp;Shuai Shao MD,&nbsp;Gang Wang MD","doi":"10.1016/j.jaci.2024.09.030","DOIUrl":"10.1016/j.jaci.2024.09.030","url":null,"abstract":"<div><h3>Background</h3><div>Bullous pemphigoid (BP) is an autoimmune blistering disease characterized by the presence of pathogenic autoantibodies and a substantial influx of immune cells into skin lesions. However, the role of eosinophils in BP remains inadequately elucidated.</div></div><div><h3>Objective</h3><div>We sought to determine the pathologic involvement of eosinophils and eosinophil extracellular traps (EETs) in BP.</div></div><div><h3>Methods</h3><div>Human samples collected from BP patients and healthy controls were utilized to explore the potential role of eosinophils and their EETs in BP patients through serologic detection, flow cytometry, and immunofluorescence. Naive CD4⁺ T cells isolated from healthy donors were stimulated and subjected to further analysis via RNA sequencing. We additionally evaluated the potential of targeting EETs in BP180-immunized BP-like mice and in <em>in vitro</em> settings.</div></div><div><h3>Results</h3><div>We found that elevated levels of eosinophils and EETs in BP patients correlated with disease severity. The DNA components within EETs played a crucial role in driving the differentiation of naive CD4⁺ T cells into follicular helper T (Tfh) cells by activating coil domains containing 25 (CCDC25). Treatment with DNase I, which disrupts the structural integrity of EETs, or neutralizing antibody against CCDC25 reduced the expansion of Tfh cells and suppressed the production of autoantibodies in BP180-immunized BP-like mouse models. Additionally, we discovered that EETs induced the <em>N</em>⁶-methyladenosine methylation of the transcription factor musculoaponeurotic fibrosarcoma (MAF) via the DNA-CCDC25-VIRMA pathway, thereby enhancing its mRNA stability and promoting Tfh cell differentiation.</div></div><div><h3>Conclusion</h3><div>Our study revealed a previously unrecognized mechanism by which EETs trigger abnormal Tfh cell differentiation through CCDC25, followed by Vir-like m⁶A methyltransferase–associated protein (VIRMA)-mediated <em>N</em>⁶-methyladenosine modification of MAF. These insights provide promising avenues for the development of targeted therapeutic interventions in the field of BP and potentially other autoimmune diseases.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 4","pages":"Pages 1357-1370"},"PeriodicalIF":11.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567337","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}