Journal of Allergy and Clinical Immunology最新文献

{"title":"From rare to more common: The emerging role of omics in improving understanding and treatment of severe inflammatory and hyperinflammatory conditions","authors":"Salla Keskitalo PhD ,&nbsp;Mikko R.J. Seppänen MD, PhD ,&nbsp;Antonio del Sol PhD ,&nbsp;Markku Varjosalo PhD","doi":"10.1016/j.jaci.2025.02.011","DOIUrl":"10.1016/j.jaci.2025.02.011","url":null,"abstract":"<div><div>Inflammation is a pathogenic driver of many diseases, including atherosclerosis and rheumatoid arthritis. Hyperinflammation can be seen as any inflammatory response that is deleterious to the host, regardless of cause. In medicine, hyperinflammation is defined as severe, deleterious, and fluctuating systemic or local inflammation with presence of a cytokine storm. It has been associated with rare autoinflammatory disorders. However, advances in omics technologies, including genomics, proteomics, and metabolomics, have revealed it to be more common, occurring in sepsis and severe coronavirus disease 2019. With a focus on proteomics, this review highlights the key role of omics in this shift. Through an exploration of research, we present how omics technologies have contributed to improved diagnostics, prognostics, and targeted therapeutics in the field of hyperinflammation. We also discuss the integration of advanced technologies, multiomics approaches, and artificial intelligence in analyzing complex datasets to develop targeted therapies, and we address their potential for revolutionizing the clinical aspects of hyperinflammation. We emphasize personalized medicine approaches for effective treatments and outline challenges, including the need for standardized methodologies, robust bioinformatics tools, and ethical considerations regarding data privacy. This review aims to provide a comprehensive overview of the molecular mechanisms underpinning hyperinflammation and underscores the potential of omics technologies in enabling successful clinical management.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 5","pages":"Pages 1435-1450"},"PeriodicalIF":11.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468183","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":"Evaluating hypogammaglobulinemia after CD19 CAR T-cell therapy","authors":"Pui-Ying Leong MD ,&nbsp;Poi Kuo BA ,&nbsp;James Cheng-Chung Wei MD, PhD","doi":"10.1016/j.jaci.2025.02.019","DOIUrl":"10.1016/j.jaci.2025.02.019","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 5","pages":"Pages 1687-1688"},"PeriodicalIF":11.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634020","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":"Is dupilumab use in atopic dermatitis associated with cutaneous T-cell lymphoma?","authors":"Peck Y. Ong MD","doi":"10.1016/j.jaci.2025.02.002","DOIUrl":"10.1016/j.jaci.2025.02.002","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 5","pages":"Pages 1481-1482"},"PeriodicalIF":11.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425382","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":"CME Calendar-AAAAI","authors":"","doi":"10.1016/S0091-6749(25)00341-0","DOIUrl":"10.1016/S0091-6749(25)00341-0","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 5","pages":"Pages A35-A36"},"PeriodicalIF":11.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143903700","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":"Dysregulation of airway and systemic interferon responses promotes asthma exacerbations in urban children","authors":"Courtney L. Gaberino MD ,&nbsp;Matthew C. Altman MD ,&nbsp;Michelle A. Gill MD, PhD ,&nbsp;Leonard B. Bacharier MD ,&nbsp;Rebecca S. Gruchalla MD, PhD ,&nbsp;George T. O’Connor MD ,&nbsp;Rajesh Kumar MD ,&nbsp;Gurjit K. Khurana Hershey MD, PhD ,&nbsp;Meyer Kattan MD ,&nbsp;Andrew H. Liu MD ,&nbsp;Stephen J. Teach MD ,&nbsp;Edward M. Zoratti MD ,&nbsp;Patrice M. Becker MD ,&nbsp;Alkis Togias MD ,&nbsp;Cynthia Visness PhD ,&nbsp;James E. Gern MD ,&nbsp;William W. Busse MD ,&nbsp;Daniel J. Jackson MD","doi":"10.1016/j.jaci.2024.12.1090","DOIUrl":"10.1016/j.jaci.2024.12.1090","url":null,"abstract":"<div><h3>Background</h3><div>Determining why some upper respiratory illnesses provoke asthma exacerbations remains an unmet need.</div></div><div><h3>Objective</h3><div>We sought to identify transcriptome-wide gene expression changes associated with colds that progress to exacerbation.</div></div><div><h3>Methods</h3><div>Two hundred eight urban children (6-17 years) with exacerbation-prone asthma were prospectively monitored for up to 2 cold illnesses. Exacerbation illnesses (Ex⁺), defined as colds leading to asthma exacerbations requiring systemic corticosteroids within 10 days, were compared to colds that resolved without exacerbation (Ex⁻). Peripheral blood and nasal lavage samples were collected at baseline and during colds for RNA sequencing. Interferon gene expression was compared between Ex⁺ and Ex⁻ illnesses. Generalized additive modeling revealed interferon response kinetics. Multiple linear regression models compared interferon expression to clinical variables.</div></div><div><h3>Results</h3><div>One hundred six participants were evaluated during 154 colds. There was greater upregulation of differentially expressed interferon genes during Ex⁺ illnesses compared to Ex⁻. Ex⁺ illnesses had greater average and steeper rise in interferon expression. Within 3 days of illness, interferon expression was positively associated with nasal rhinovirus quantity (nasal: adjusted <em>R</em>² = 0.48, <em>P</em> = .015; blood: adjusted <em>R</em>² = 0.22, <em>P</em> = .013), and interferon expression was negatively associated with percentage predicted forced expiratory volume in 1 second (nasal: β = −0.010, <em>P</em> = .048; blood: β = −0.008, <em>P</em> = .023). Participants with lower baseline interferon expression had shorter time to exacerbation, higher risk for exacerbation with viral illnesses, and greater increase in interferon expression during viral colds (nasal: β = −0.80, <em>P</em> &lt; .0001; blood: β = −0.75, <em>P</em> &lt; .0001).</div></div><div><h3>Conclusion</h3><div>Dysregulated interferon responses are important contributors to asthma exacerbation risk in children. Low baseline interferon expression followed by greater upregulation of interferon pathways in airway and blood during respiratory illnesses increased exacerbation risk. Targeting this pathway in at-risk individuals holds promise for the personalized prevention of asthma exacerbations.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 5","pages":"Pages 1499-1509"},"PeriodicalIF":11.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949110","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":"The evolving prostaglandin E2 story in chronic sinus disease","authors":"Joshua A. Boyce MD ,&nbsp;Jun Nagai PhD","doi":"10.1016/j.jaci.2024.12.1093","DOIUrl":"10.1016/j.jaci.2024.12.1093","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 5","pages":"Pages 1475-1477"},"PeriodicalIF":11.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977748","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 efficacy and mechanisms of biologics for chronic rhinosinusitis with nasal polyps","authors":"Radomir Kratchmarov MD, PhD,&nbsp;Tiffany Dharia MD,&nbsp;Kathleen Buchheit MD","doi":"10.1016/j.jaci.2025.03.011","DOIUrl":"10.1016/j.jaci.2025.03.011","url":null,"abstract":"<div><div>The management of chronic rhinosinusitis with nasal polyps (CRSwNP) can be challenging, particularly when standard treatments including intranasal corticosteroids and endoscopic sinus surgery do not result in adequate symptom control. CRSwNP is frequently characterized by a type 2 immune signature, and many patients have other comorbid type 2 conditions, including asthma. There are currently 3 biologic therapies approved for the treatment of CRSwNP—omalizumab, mepolizumab, and dupilumab—and there are promising therapies in development. Biologic therapies allow for improved patient quality of life in CRSwNP, reduction in need for systemic corticosteroid treatment and endoscopic sinus surgery, and improvement in treatment of comorbidities. Translational studies assessing how biologic therapies can modify inflammation in CRSwNP have allowed for a greater understanding of CRSwNP pathogenesis. We review CRSwNP clinical trial and real-world data on the effectiveness and safety of biologics, discuss their therapeutic mechanisms, assess outcomes of biologic therapy versus endoscopic sinus surgery, and discuss therapies in development and future directions.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 5","pages":"Pages 1401-1410"},"PeriodicalIF":11.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709339","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":"Identification of bronchial epithelial genes associated with type 2 eosinophilic inflammation in asthma","authors":"Stephane Esnault PhD ,&nbsp;Kimberly A. Dill-McFarland PhD ,&nbsp;Matthew C. Altman MD ,&nbsp;Melissa A. Rosenkranz PhD ,&nbsp;Nizar N. Jarjour MD ,&nbsp;William W. Busse MD","doi":"10.1016/j.jaci.2024.12.1089","DOIUrl":"10.1016/j.jaci.2024.12.1089","url":null,"abstract":"<div><h3>Background</h3><div>Airway inflammation plays a critical role in asthma pathogenesis and pathophysiology, but the molecular pathways contributing to airway inflammation are not fully known, particularly type 2 (T2) inflammation characterized by both eosinophilia and higher fractional exhaled nitric oxide (F<span>eno</span>) levels.</div></div><div><h3>Objective</h3><div>We sought to identify genes whose level of expression in epithelial brushing samples were associated with both bronchoalveolar lavage (BAL) eosinophilia and generation of F<span>eno</span>.</div></div><div><h3>Methods</h3><div>We performed segmental allergen bronchoprovocation (SBP-Ag) in participants with asthma, then RNA sequencing analyses of BAL cells and brushing samples before and 48 hours after SBP-Ag to identify regulation of eosinophil recruitment and F<span>eno</span> changes.</div></div><div><h3>Results</h3><div>Allergen bronchoprovocation increased F<span>eno</span> levels, which correlated with eosinophilia. Thirteen genes were identified in brushing samples, whose expression changed in response to SBP-Ag and correlated with both airway eosinophilia and F<span>eno</span> levels after SBP-Ag. Among these 13 genes, epithelial cell product CDH26/cadherin-26 contributed to the amplification of T2 inflammation, as reflected by eosinophilia and F<span>eno</span>, and causal mediation analyses with pro-T2 and proeosinophilic cytokine mediators in BAL fluids. Among the genes associated with reduced eosinophilia and F<span>eno</span>, <em>HEY2</em> is known to enhance cell proliferation, migration, invasion, and epithelial-to-mesenchymal transition, as well as to reduce apoptosis.</div></div><div><h3>Conclusion</h3><div>This unbiased RNA sequencing analysis in participants with allergic asthma revealed several epithelial cell genes, particularly <em>CDH26,</em> that may be critical for the development or augmentation of T2 inflammation in asthma.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 5","pages":"Pages 1510-1520"},"PeriodicalIF":11.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142964682","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":"Structural determinants of peanut-induced anaphylaxis","authors":"Scott A. Smith MD, PhD ,&nbsp;Rebecca A. Shrem MS ,&nbsp;Bruno B.C. Lança BS ,&nbsp;Jian Zhang MS ,&nbsp;Joyce J.W. Wong PhD ,&nbsp;Derek Croote PhD ,&nbsp;R. Stokes Peebles Jr. MD ,&nbsp;Benjamin W. Spiller PhD","doi":"10.1016/j.jaci.2024.12.1095","DOIUrl":"10.1016/j.jaci.2024.12.1095","url":null,"abstract":"<div><h3>Background</h3><div>Human IgE mAbs recognizing peanut allergens have recently become available, but we lack a detailed understanding of how these IgEs target allergens.</div></div><div><h3>Objective</h3><div>We sought to determine the molecular details of the antibody-allergen interaction for a panel of clinically important human IgE mAbs and to develop strategies to disrupt disease causing antibody-allergen interactions.</div></div><div><h3>Methods</h3><div>We identified candidates from a panel of epitope binned human IgE mAbs that recognize 2 important and homologous peanut allergens, Ara h 2 and Ara h 6. Crystal structures were determined revealing the interfaces (antigenic sites) of exemplars of 5 common IgE bins.</div></div><div><h3>Results</h3><div>Among the common antigenic sites on Ara h 2 and Ara h 6, 2 sites (A and B) are highly conserved between the allergens, explaining the cross-reactivity of antibodies that recognize these sites. Three sites (C, D, and F) involve residues that are not conserved between the allergens. Of the 5 common sites, 3 sites (B, C, and D) involve residues that are near each other only when the allergens are properly folded, such that these sites are conformational. Two additional sites (sites A and F) involve largely linear stretches of amino acids. Site F targeted antibody, 38B7, binds to a peptide sequence DPYSP^OHS, in which hydroxylation of the last proline is critical for binding. This sequence is repeated 2 or 3 times depending on the Ara h 2 isoform, enabling 38B7 to induce anaphylaxis as a single mAb, without a second antibody. We have mutated key residues in each site and created a panel of hypoallergens, having reduced IgE mAb binding and lacking the ability to induce anaphylaxis in our murine model.</div></div><div><h3>Conclusion</h3><div>We created a structural map of the IgE antibody response to the most important peanut allergen proteins to enable the design of new allergy immunotherapies and vaccines.</div></div>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"155 5","pages":"Pages 1547-1556.e3"},"PeriodicalIF":11.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142978423","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":"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}