Journal of Allergy and Clinical Immunology最新文献

{"title":"Curation of gene–disease relationships in primary antibody deficiencies using the ClinGen validation framework","authors":"Alejandro Nieto-Patlán PhD ,&nbsp;Justyne Ross PhD ,&nbsp;Shruthi Mohan PhD ,&nbsp;Michelle K. Paczosa PhD ,&nbsp;Rasha Soliman MBBS ,&nbsp;Olga Sarmento PhD ,&nbsp;Ermal Aliu MD ,&nbsp;Lavvina Thiyagarajan MBBS ,&nbsp;Anita Chandra MRCP, FRCPath, PhD ,&nbsp;Capucine Picard MD, PhD ,&nbsp;Klaus Warnatz MD ,&nbsp;Stephen Jolles MD, PhD ,&nbsp;Harry Lesmana MD ,&nbsp;Paul J. Maglione MD, PhD ,&nbsp;Craig D. Platt MD, PhD ,&nbsp;Anna Sediva MD ,&nbsp;Kathleen E. Sullivan MD, PhD ,&nbsp;Kejian Zhang MD ,&nbsp;Forum Raval PhD ,&nbsp;Stuart G. Tangye PhD ,&nbsp;Roshini S. Abraham PhD","doi":"10.1016/j.jaci.2025.01.005","DOIUrl":"10.1016/j.jaci.2025.01.005","url":null,"abstract":"<div><h3>Background</h3><div>The Clinical Genome Resource (ClinGen) is an international collaborative effort among scientists and clinicians, diagnostic and research laboratories, and the patient community. Using a standardized framework, ClinGen has established guidelines to classify gene–disease relationships as definitive, strong, moderate, and limited on the basis of available scientific and clinical evidence. When the genetic and functional evidence for a gene–disease relationship has conflicting interpretations or contradictory evidence, they can be disputed or refuted.</div></div><div><h3>Objective</h3><div>We assessed genes related to primary antibody deficiencies.</div></div><div><h3>Methods</h3><div>The ClinGen Antibody Deficiencies Gene Curation Expert Panel, using the ClinGen framework, classified genes related to primary antibody deficiency that primarily affect B-cell development and/or function, and that account for the largest proportion of inborn errors of immunity or primary immunodeficiencies.</div></div><div><h3>Results</h3><div>The expert panel curated a total of 65 genes associated with humoral immune defects to validate 74 gene–disease relationships. Of these, 40 were classified as definitive, 1 as strong, 16 as moderate, 15 as limited, and 2 as disputed. The curation process involved reviewing 490 patient records and 3546 associated human phenotype ontology entries. The 3 most frequently observed terms related to primary antibody deficiency were <em>decreased circulating antibody level, pneumonia,</em> and <em>lymphadenopathy.</em></div></div><div><h3>Conclusions</h3><div>These curations (publicly available at <span><span>ClinicalGenome.org</span><svg><path></path></svg></span>) represent the first effort to provide a comprehensive genetic and phenotypic revision of genetic disorders affecting humoral immunity, as reviewed and approved by experts in the field.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 5","pages":"Pages 1647-1663"},"PeriodicalIF":11.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991743","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":"Longitudinal integrated proteomic and metabolomic skin changes in patients with atopic dermatitis treated with dupilumab","authors":"Elena Goleva PhD ,&nbsp;Evgeny Berdyshev PhD ,&nbsp;Simion Kreimer PhD ,&nbsp;Julie A. Reisz PhD ,&nbsp;Angelo D’Alessandro PhD ,&nbsp;Irina Bronova PhD ,&nbsp;Taras Lyubchenko PhD ,&nbsp;Brittany N. Richers BS ,&nbsp;Clifton F. Hall MS ,&nbsp;Olivia Xiao BS ,&nbsp;Anna-Sofia Bronoff BS ,&nbsp;Shantanu Bafna MS ,&nbsp;Inoncent Agueusop PhD ,&nbsp;Emilie Gloaguen PhD ,&nbsp;Joseph Zahn MD ,&nbsp;Robert Bissonnette MD ,&nbsp;Annie Zhang MD ,&nbsp;Donald Y.M. Leung MD, PhD","doi":"10.1016/j.jaci.2025.01.020","DOIUrl":"10.1016/j.jaci.2025.01.020","url":null,"abstract":"<div><h3>Background</h3><div>Inhibition of IL-4/IL-13–driven inflammation by dupilumab has shown significant clinical benefits in treatment of atopic dermatitis (AD).</div></div><div><h3>Objective</h3><div>Our aim was to assess longitudinal protein and metabolite composition in AD skin during dupilumab treatment.</div></div><div><h3>Methods</h3><div>Skin tape strips (STSs) were collected from lesional/nonlesional skin of 20 patients with AD during a 16-week dupilumab treatment course and from 20 healthy volunteers (HVs) followed for 16 weeks. STS extracts were examined by liquid chromatography–mass spectrometry proteomic analysis and targeted metabolomics.</div></div><div><h3>Results</h3><div>Approximately 2500 individual proteins were identified in the STS extracts. Of those proteins, 490 were present in at least 80% of the AD and HV skin samples and differentially expressed in the AD skin; the levels of 249 proteins were significantly reduced (cluster 1), and the levels of 136 were significantly increased (cluster 2) in the AD skin versus in the HV skin (both <em>P</em> &lt; .0001). Functionally, cluster 1 included proteins involved in epidermal barrier formation, lysosomal enzymes required for lamellae assembly, and oxidative response. Cluster 2 was enriched for markers of epidermal hyperplasia, glycolytic enzymes, and actin filament proteins. A significant increase in cluster 1 and a significant inhibition of cluster 2 proteins expression were achieved in AD skin by 16 weeks of dupilumab treatment (<em>P</em> &lt; .0001 for both vs baseline), approaching the levels in HV skin. These improvements were also revealed in differential metabolite changes in the STS extracts, including amino acids, nucleotide breakdown products, and antioxidants.</div></div><div><h3>Conclusion</h3><div>Longitudinal integrated assessment of the skin proteome and metabolome in patients with AD who were treated with dupilumab established significant inhibition of epidermal hyperplasia and improvement in epidermal differentiation. The identified changes were linked to improvements in clinical AD skin assessments, including improvements in transepidermal water loss and disease severity.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 5","pages":"Pages 1536-1546"},"PeriodicalIF":11.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038984","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":"Innate immune function in chronic rhinosinusitis","authors":"Robert J. Lee PhD ,&nbsp;Noam A. Cohen MD, PhD","doi":"10.1016/j.jaci.2025.01.022","DOIUrl":"10.1016/j.jaci.2025.01.022","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 5","pages":"Pages 1472-1474"},"PeriodicalIF":11.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065504","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":"Clinical, immunologic, and genetic characteristics of 148 patients with natural killer cell deficiency","authors":"Manar Abdalgani MBBS ,&nbsp;Evelyn R. Hernandez MPH ,&nbsp;Luis A. Pedroza PhD ,&nbsp;Ivan K. Chinn MD ,&nbsp;Lisa R. Forbes Satter MD ,&nbsp;Nicholas L. Rider DO ,&nbsp;Pinaki P. Banerjee PhD ,&nbsp;M. Cecilia Poli MD, PhD ,&nbsp;Sanjana Mahapatra PhD ,&nbsp;Debra Canter MS ,&nbsp;Tram Cao MS ,&nbsp;Linda M. Shawver BS ,&nbsp;Sarada L. Nandiwada PhD ,&nbsp;James R. Lupski MD, PhD ,&nbsp;Jennifer E. Posey MD, PhD ,&nbsp;Rajasekhar Ramakrishnan EngScD ,&nbsp;Emily M. Mace PhD ,&nbsp;Jordan S. Orange MD, PhD","doi":"10.1016/j.jaci.2025.01.030","DOIUrl":"10.1016/j.jaci.2025.01.030","url":null,"abstract":"<div><h3>Background</h3><div>Natural killer (NK) cell deficiency (NKD) is an immunodeficiency phenotype in which abnormality of NK cells is the major clinically relevant immune defect.</div></div><div><h3>Objective</h3><div>We sought to define the clinical, immunologic, and genetic characteristics of patients with NKD to aid in the understanding of these individuals and this cell type and guide future research and clinical practice.</div></div><div><h3>Methods</h3><div>During 2006-2022, 168 individuals with a suspected diagnosis of NKD were enrolled, with comprehensive clinical, immunologic, and genetic data collected and analyzed. Research exome sequencing was performed to identify both known and novel genetic associations.</div></div><div><h3>Results</h3><div>NK cell abnormalities consistent with NKD were confirmed in 148 participants. Most presented during childhood (median age 13 years, range 0-76 years), though 34% were adults. All tested individuals exhibited reduced NK cell cytotoxic function; 44% also had decreased NK cell numbers and/or mature NK cells. Herpesvirus and/or papillomavirus infections were observed in 71%, malignancies were observed in 7%, and a 5% case-fatality rate was noted. Among the 99 participants who underwent research exome sequencing, 29% were considered solved for a likely contributing variant allele, with 52% of these cases involving known genes and 48% involving novel genes.</div></div><div><h3>Conclusions</h3><div>NKD is a phenotypic immunodeficiency associated with increased susceptibility to certain viral infections and cancer with multiple genetic etiologies, revealing key biological pathways for NK cell development and function. This research underscores the role of NK cells in human immune defenses and helps advance the identification of at-risk populations, precise genetic diagnoses, and informed clinical management for patients with NKD.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 5","pages":"Pages 1623-1634"},"PeriodicalIF":11.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364774","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":"Getting to know adenosine deaminase 2 deficiency inside and out","authors":"Lisa Ehlers MD, PhD ,&nbsp;Isabelle Meyts MD, PhD","doi":"10.1016/j.jaci.2025.01.040","DOIUrl":"10.1016/j.jaci.2025.01.040","url":null,"abstract":"<div><div>Ten years after the description of the first cohorts of patients with adenosine deaminase (ADA2) deficiency (DADA2), the pathomechanisms underlying the disease on a cellular level remain poorly understood. With the establishment of the lysosomal localization of the ADA2 protein and its involvement in nucleic acid sensing, the pathophysiologic focus has shifted to the inside of the cell. At the same time, extracellular (serum) ADA2 enzyme activity continues to be the diagnostic reference standard in patients with suspected DADA2. The diverse clinical phenotype and weak genotype–phenotype correlations further complicate the identification of shared cellular mechanisms that cause inflammation, immunodeficiency, and bone marrow failure in the absence of functional ADA2. This review inspects the characteristics of the ADA2 protein and its proposed function. The latter is discussed in the context of possible mechanisms driving the clinical phenotype in patients lacking functional ADA2. We discuss established processes and introduce unexplored pathways in the pathogenesis of DADA2.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 5","pages":"Pages 1451-1463"},"PeriodicalIF":11.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433119","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":"Molecular mimicry-driven autoimmunity in chronic rhinosinusitis with nasal polyps","authors":"Tomoaki Asamori MD, PhD ,&nbsp;Hiroto Katoh MD, PhD ,&nbsp;Mikiya Takata MD ,&nbsp;Daisuke Komura MD, PhD ,&nbsp;Miwako Kakiuchi MD, PhD ,&nbsp;Itaru Hashimoto MD, PhD ,&nbsp;Madoka Sakurai MD ,&nbsp;Asami Yamamoto MS ,&nbsp;Takeshi Tsutsumi MD, PhD ,&nbsp;Takahiro Asakage MD, PhD ,&nbsp;Yasushi Ota MD, PhD ,&nbsp;Shumpei Ishikawa MD, PhD","doi":"10.1016/j.jaci.2025.02.014","DOIUrl":"10.1016/j.jaci.2025.02.014","url":null,"abstract":"<div><h3>Background</h3><div>The pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) remains a subject of discussion. Although both microbial infection and autoimmunity have been proposed as potential contributors to CRSwNP pathobiology, their respective roles and intricate interactions in disease progression remain unclear owing to the limited knowledge regarding dysregulated humoral immunity in CRSwNP.</div></div><div><h3>Objective</h3><div>To deepen understanding of CRSwNP, we sought to identify the precise humoral antigens targeted by dominant B-cell clones within the disease environments.</div></div><div><h3>Methods</h3><div>Immunoglobulin repertoire sequencing was performed to identify dominant B-cell clones in CRSwNP tissues. These immunoglobulin clones were reconstructed as antibodies, which were then used in immunoprecipitation and antigen array experiments for hypothesis-free global antigen profiling of autogenous and exogenous antigens.</div></div><div><h3>Results</h3><div>From analysis of 13 patients with CRSwNP, 31 antibodies were reconstructed from dominant B-cell clones identified in 9 patients. Seven novel protein autoantigens were identified, 5 of which were nucleic acid–binding proteins, and all were associated with autoimmune diseases. Additionally, 9 microbial antigens, including various viruses, bacteria, and fungi, were discovered. Notably, 2 antibodies demonstrated dual reactivity, simultaneously recognizing both microbial and human proteins. For example, 1 antibody targeted cytomegalovirus, <em>Clostridium tetani</em>, and human PLEC, whereas another recognized <em>Aspergillus niger</em> and human DLAT, through molecular mimicry of shared amino acid homologies.</div></div><div><h3>Conclusion</h3><div>Our data indicate the possibility that the pathobiology of CRSwNP involves autoreactive humoral immunity, with a subset of cases potentially exhibiting molecular mimicry–driven autoimmune features triggered by microbial infections. Nevertheless, this hypothesis requires further investigation.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 5","pages":"Pages 1521-1535"},"PeriodicalIF":11.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472273","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 & Notes-AAAAI","authors":"","doi":"10.1016/S0091-6749(25)00340-9","DOIUrl":"10.1016/S0091-6749(25)00340-9","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 5","pages":"Pages A32-A33"},"PeriodicalIF":11.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143903699","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":"TL1A, a novel alarmin in airway, intestinal, and autoimmune disorders","authors":"Gilda Varricchi MD, PhD ,&nbsp;Remo Poto MD, PhD ,&nbsp;Gjada Criscuolo MSci, PhD ,&nbsp;Caterina Strisciuglio MD, PhD ,&nbsp;Parameswaran Nair MD, PhD ,&nbsp;Gianni Marone MD","doi":"10.1016/j.jaci.2025.02.018","DOIUrl":"10.1016/j.jaci.2025.02.018","url":null,"abstract":"<div><div>The term <em>alarmin</em> denotes a broad class of molecules rapidly released to alert the immune system through the engagement of specific receptors on immune cells. Three alarmin cytokines—thymic stromal lymphopoietin, IL-33, and IL-25—are released from epithelial and certain stromal cells. TNF-like cytokine 1A (TL1A) is a member of the TNF cytokine superfamily, first identified in human endothelial cells. TL1A is now considered a novel alarmin expressed by human and mouse bronchial and intestinal epithelial cells. TL1A exerts its biological activities by binding to a trimeric receptor DR3 (death receptor 3), expressed on a wide spectrum of immune and structural cells, including lung fibroblasts, endothelial cells, and bronchial epithelial cells. TL1A has been implicated in experimental and human inflammatory bowel diseases as well as in airway inflammation and remodeling in severe asthma. A monoclonal antibody anti-TL1A (tulisokibart) is effective in inducing clinical remission in ulcerative colitis patients. Increasing evidence suggests that TL1A is also involved in certain autoimmune disorders, such as rheumatoid arthritis and psoriasis. These emerging findings broaden the role of TL1A in various human inflammatory conditions. Several clinical trials are currently evaluating the safety and efficacy of monoclonal antibodies targeting TL1A in asthma or inflammatory bowel disease patients.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 5","pages":"Pages 1420-1434"},"PeriodicalIF":11.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515825","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":"Epicutaneous immunotherapy with VIASKIN patch for peanut allergy: Permeability via intact skin","authors":"Christophe Dupont MD ,&nbsp;Hugh A. Sampson MD","doi":"10.1016/j.jaci.2025.01.038","DOIUrl":"10.1016/j.jaci.2025.01.038","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 5","pages":"Pages 1682-1683"},"PeriodicalIF":11.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567162","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,&nbsp;Lucyna Mastalerz MD, PhD","doi":"10.1016/j.jaci.2025.02.009","DOIUrl":"10.1016/j.jaci.2025.02.009","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 5","pages":"Page 1686"},"PeriodicalIF":11.4,"publicationDate":"2025-05-01","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}