Journal of Allergy and Clinical Immunology最新文献

{"title":"Techniques and analytic workflow for spatial transcriptomics and its application to allergy and inflammation.","authors":"Haihan Zhang, Matthew T Patrick, Jingyu Zhao, Xintong Zhai, Jialin Liu, Zheng Li, Yiqian Gu, Joshua Welch, Xiang Zhou, Robert Modlin, Lam C Tsoi, Johann E Gudjonsson","doi":"10.1016/j.jaci.2025.01.009","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.01.009","url":null,"abstract":"<p><p>Spatial profiling, through single-cell gene level expression data paired with cell localization, offers unprecedented biological insights within the intact spatial context of cells in healthy and diseased tissue, adding a novel dimension to data interpretation. This review summarizes recent developments in this field, its application to allergy and inflammation, and recent single-cell resolution platforms designed for spatial transcriptomics with a focus on data processing and analyses for efficient biological interpretation of data. By preserving spatial context, these technologies provide critical insights into tissue architecture and cellular interactions unattainable with traditional transcriptomics methods, such as revealing localized inflammatory cell network in atopic dermatitis, and T-cell interactions in the lung in chronic obstructive pulmonary disease. Spatial profiling offers opportunities for discovering novel biomarkers, defining compartmentalization of immune responses within tissues and individual diseases, and accelerating novel discoveries towards a greater understanding of fundamental disease mechanisms, and eventually towards the development of future targeted therapies.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005911","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":"Respiratory mucosal plasma exudation in human innate and adaptive immunity.","authors":"Carl Persson","doi":"10.1016/j.jaci.2025.01.011","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.01.011","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"46 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991744","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":"Primary Antibody Deficiencies: Curation Of Gene-Disease Relationships Using A ClinGen Validation Framework.","authors":"Alejandro Nieto-Patlán,Justyne Ross,Shruthi Mohan,Michelle K Paczosa,Rasha Soliman,Olga Sarmento,Ermal Aliu,Lavvina Thiyagarajan,Anita Chandra,Capucine Picard,Klaus Warnatz,Stephen Jolles,Harry Lesmana,Paul J Maglione,Craig D Platt,Anna Sediva,Kathleen E Sullivan,Kejian Zhang,Forum Raval,Stuart G Tangye,Roshini S Abraham","doi":"10.1016/j.jaci.2025.01.005","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.01.005","url":null,"abstract":"BACKGROUNDThe Clinical Genome Resource (ClinGen) is an international collaborative effort between scientists and clinicians, diagnostic and research laboratories as well as the patient community. Using a standardized framework, ClinGen has established guidelines to classify gene-disease relationships as Definitive, Strong, Moderate, and Limited based on 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.OBJECTIVES AND METHODSThe ClinGen Antibody Deficiencies Gene Curation Expert Panel (AD-GCEP), using the ClinGen framework, has classified genes related to Primary Antibody Deficiencies (PAD) that primarily affect B cell development and/or function and accounts for the largest proportion of Inborn Errors of Immunity (IEI) or Primary Immunodeficiencies (PIDs).RESULTSThe AD-GCEP curated a total of 65 genes associated with humoral immune defects to validate 74 gene-disease relationships. Of these, 40 gene-disease relationships were classified as Definitive, 1 as Strong, 16 as Moderate, 15 as Limited, and two as Disputed. The curation process involved the review of 490 patient records and 3,546 associated Human Phenotype Ontology (HPO) entries. The most frequently observed HPO terms related to PAD was decreased circulating antibody (Ab) level, pneumonia and lymphadenopathy.CONCLUSIONSThese curations represent the first effort by the Immunology Clinical Domain Working Group (CDWG) of ClinGen to provide a comprehensive genetic and phenotypic revision of genetic disorders affecting humoral immunity, and these were reviewed and approved by experts in the field. The curations are publicly available at www.clinicalgenome.org.","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"37 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-01-16","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":"Corrigendum.","authors":"","doi":"10.1016/j.jaci.2025.01.004","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.01.004","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005908","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":"Antigenic determinants underlying IgE-mediated anaphylaxis to peanut.","authors":"Scott A Smith,Yasmin W Khan,Rebecca A Shrem,Jonathan A Hemler,Joshua E Doyle,Jacob Daniel,Jian Zhang,Glorismer Pena-Amelunxen,Lorenz Aglas,Robert G Hamilton,Robert Getts,Hugh A Sampson,Joyce J W Wong,Derek Croote,R Stokes Peebles,Benjamin W Spiller","doi":"10.1016/j.jaci.2024.12.1094","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.12.1094","url":null,"abstract":"BACKGROUNDStudies of human IgE and its targeted epitopes on allergens have been very limited. We have an established method to immortalize IgE encoding B cells from allergic individuals.OBJECTIVETo develop an unbiased and comprehensive panel of peanut-specific human IgE mAbs to characterize key immunodominant antigenic regions and epitopes on peanut allergens to map the molecular interactions responsible for inducing anaphylaxis.METHODSUsing human hybridoma technology to immortalize IgE encoding B cells from peripheral blood of subjects with severe peanut allergy, we generated a panel of naturally occurring human IgE mAbs in an unbiased manner. Isolated IgE mAbs were characterized extensively in allergen binding assays, peptide array analysis, antigenic mapping, binding kinetic analysis, serum blocking, skin testing inhibition, and functional assessment using human FcεRI transgenic mice.RESULTSWe created a large panel of 54 peanut-specific IgE mAbs, of which 63% were specific for Ara h 2 and/or 6. Pairs of IgE mAbs with the same antigen-specificity but different binding sites were able to mediate passive systemic anaphylaxis in FcεRI transgenic mice. A single mAb targeting the repetitive motif on Ara h 2 was able to induce degranulation and anaphylaxis on its own. IgG1 switched-variant immunoglobulins of the IgE mAb inhibited patients´ IgE binding to peanut extract between 30-60% (ImmunoCAP) and reduced peanut extract-induced skin wheal sizes by 1.6-7.4 millimeters in peanut allergic patients.CONCLUSIONWe created a molecular map of the IgE antibody response to the most important peanut allergen proteins to enable the design of new allergy immunotherapies and vaccines.","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"15 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142989380","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 relationship between the early life gastrointestinal microbiome and childhood nocturnal cough.","authors":"Amy A Eapen,Tengfei Ma,Alexandra R Sitarik,Ze Meng,Dennis R Ownby,Andrea E Cassidy-Bushrow,Ganesa Wegeinka,Edward M Zoratti,Susan V Lynch,Christine C Johnson,Albert M Levin","doi":"10.1016/j.jaci.2025.01.006","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.01.006","url":null,"abstract":"BACKGROUNDNocturnal cough affects approximately 1 in 3 children, can negatively impact child health, and is often attributable to asthma. The association of the gut microbiome with nocturnal cough has not been investigated.OBJECTIVETo investigate the association between early-life gut microbiome composition and nocturnal cough overall and in the context of asthma.METHODSGut microbiota 1-month (neonate) and 6-month (infant) specimens from 512 children in the Wayne County, Health, Environment, Allergy, and Asthma Longitudinal Study were profiled using 16S rRNA V4 sequencing. Nocturnal cough (parental-report) and asthma (parental-reported doctor diagnosis) were assessed at age 4 years. Microbiome Regression-Based Kernel Association Tests were used to assess the relationship between gut microbiota composition and nocturnal cough overall and in the context of asthma. Operational taxonomic unit (OTU) associations were conducted using negative binomial regression, adjusting for multiple comparisons using the false discovery rate (FDR).RESULTSStool microbial composition differences during infancy were associated with nocturnal cough (Weighted Unifrac p=0.045). 78 OTUs were significantly associated with nocturnal cough overall (FDR<0.05). 110 OTUs were significantly associated with nocturnal cough and differed by asthma status (interaction FDR<0.05), with predominance of Lachnospiraceae Blautia and Dorea. 32 OTU were identified as having both overall effects and differences by asthma status. Among OTUs with significant nocturnal cough-by-asthma interactions, 84 retained significance in children with asthma, with 45 exclusive to those with asthma (predominance of Bacteroidaceae Bacteroides and Lachnospiraceae Dorea).CONCLUSIONInfantile gut microbiome development is associated with nocturnal cough and differed by asthma status by age 4 years. Further studies are needed to determine if the gut microbiome may provide additional information for the early identification of children at risk for nocturnal cough, with and without asthma.","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"97 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142989381","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":"Erratum.","authors":"","doi":"10.1016/j.jaci.2025.01.001","DOIUrl":"https://doi.org/10.1016/j.jaci.2025.01.001","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142964576","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":"Paradigms and Perspectives: The Evolving Prostaglandin E₂ Story in Chronic Sinus Disease.","authors":"Joshua A Boyce, Jun Nagai","doi":"10.1016/j.jaci.2024.12.1093","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.12.1093","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-01-11","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":"Structural determinants of peanut induced anaphylaxis.","authors":"Scott A Smith, Rebecca A Shrem, Bruno B C Lança, Jian Zhang, Joyce J W Wong, Derek Croote, R Stokes Peebles, Benjamin W Spiller","doi":"10.1016/j.jaci.2024.12.1095","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.12.1095","url":null,"abstract":"<p><strong>Background: </strong>Human monoclonal IgE antibodies recognizing peanut allergens have recently become available, but we lack a detailed understanding of how these IgEs target allergens.</p><p><strong>Objective: </strong>To determine the molecular details of the antibody-allergen interaction for a panel of clinically important human IgE monoclonal antibodies and to develop strategies to disrupt disease causing antibody-allergen interactions.</p><p><strong>Methods: </strong>We identified candidates from a panel of epitope binned human IgE monoclonals that recognize two important and homologous peanut allergens, Ara h 2 and Ara h 6. Crystal structures were determined revealing the interfaces (antigenic sites) of exemplars of five common IgE bins.</p><p><strong>Results: </strong>Among the common antigenic sites on Ara h 2 and Ara h 6, two 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 five common sites, three Sites (B, C, and D) involve residues that are only near each other 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 two or three times depending on the Ara h 2 isoform, enabling 38B7 to induce anaphylaxis as a single monoclonal, 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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-01-11","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":"Update on Mast Cell Biology.","authors":"Hadas Tamar Pahima, Daniel F Dwyer","doi":"10.1016/j.jaci.2024.12.1092","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.12.1092","url":null,"abstract":"<p><p>Mast cells (MCs) are heterogeneous tissue-resident effector cells thought to play central roles in allergic inflammatory disease, yet the degree of heterogeneity and nature of these roles has remained elusive. In recent years, advances in tissue culture systems, pre-clinical mouse models, and the continued spread of single-cell RNA sequencing has greatly advanced our understanding of MC phenotypes in health and disease. These approaches have identified novel interactions of MC subsets with immune cells, neurons, and tissue structural cells, changing our understanding of how MCs both drive and help resolve tissue inflammation, reshape tissue microenvironments, and influence host behavior. This review addresses key studies from 2022-2024 that have advanced our understanding of MC biology in mouse and human.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970840","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}