Journal of Allergy and Clinical Immunology最新文献

{"title":"Gastroesophageal reflux disease, laryngopharyngeal reflux, and vocal cord dysfunction/Inducible laryngeal obstruction - overlapping conditions that impact asthma.","authors":"Amy A Eapen,Meera R Gupta,Richard F Lockey,Philip G Bardin,Alan P Baptist","doi":"10.1016/j.jaci.2024.10.006","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.10.006","url":null,"abstract":"Asthma is a chronic lung condition that may be affected by numerous medical comorbidities. Such comorbidities can influence the presentation and even the severity of asthma. Alternatively, asthma may be misdiagnosed as a comorbidity when symptoms overlap. Three medical conditions that commonly affect asthma management are gastroesophageal reflux disease (GERD), laryngopharyngeal reflux (LPR), and vocal cord dysfunction/Inducible laryngeal obstruction (VCD/ILO). These conditions can be difficult to distinguish from one another, and from asthma itself. In the following review, the epidemiology, pathophysiology, symptomatology, and diagnostic considerations of each condition in both adult and pediatric populations are discussed. Treatment options, and how such options may influence asthma outcomes, are included. Finally, knowledge gaps are highlighted in each area, as a better understanding of the optimal diagnostic and therapeutic approaches will allow for improved individualized care of asthma patients.","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"40 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142451817","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.","authors":"Chang-Gyu Jung, Kathleen M Buchheit, Grazyna Bochenek, Emily Dzoba, Seong Ho Cho","doi":"10.1016/j.jaci.2024.10.007","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.10.007","url":null,"abstract":"<p><p>Asthma, characterized as a chronic heterogeneous airway disease, often presents with common comorbid conditions. The concept of 'one-airway-one-disease' was coined, emphasizing the connection between asthma and upper airway comorbidities (UACs) such as allergic or non-allergic rhinitis, chronic rhinosinusitis with or without nasal polyps, and aspirin/nonsteroidal anti-inflammatory drug-exacerbated respiratory disease more than 20 years ago. Since then, numerous studies demonstrate that UACs are closely related and affect asthma phenotypes. Recognizing and managing these UACs are crucial aspects of comprehensive asthma care. Addressing these conditions as part of asthma treatment can lead to better control of symptoms, improved lung function and the quality of life. Moreover, it is important to explore the field of respiratory biologics that represent the latest advancements in medical treatment options for asthma patients with UACs.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466080","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":"Altered B-cell, plasma cell and antibody immune profiles in blood of systemic mastocytosis.","authors":"Alba Pérez-Pons,Ana Henriques,Teresa Contreras Sanfeliciano,María Jara-Acevedo,Paula Navarro-Navarro,Andrés C García-Montero,Iván Álvarez-Twose,Quentin Lecrevisse,Rafael Fluxa,Laura Sánchez-Muñoz,Carolina Caldas,Julio Pozo,Óscar González-López,Martín Pérez-Andrés,Andrea Mayado,Alberto Orfao","doi":"10.1016/j.jaci.2024.10.005","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.10.005","url":null,"abstract":"BACKGROUNDSystemic mastocytosis (SM) is a heterogeneous disease characterised by an expansion of KIT-mutated constitutively activated mast cells (MC) which release MC mediators that might act on the tumour microenvironment including other immune cells.OBJECTIVEHere we investigated the blood distribution of B-cell, plasma cell (PC) and antibody-isotype compartments in SM.METHODSWe used spectral flow cytometry and the EuroFlow Immunomonitoring panel and Lymphocyte Screening Tube to quantify B-cells, PC and their subsets in blood of 108 SM patients - 35 bone marrow mastocytosis (BMM), 64 indolent SM (ISM), 9 aggressive SM (ASM)- vs 117 age-matched healthy donors (HD) and paired bone marrow (BM) samples of 31 SM vs 17 controls, respectively. In parallel, immunoglobulin (Ig) M, IgD, IgG, IgA and IgE plasma levels of were measured.RESULTSCompared to HD, SM patients showed an increased immature B-cell production in BM (P=0.003) associated with a greater release of pre-germinal center immature (P<0.001) and naive CD5+ B-lymphocytes (P<0.001) to blood, but a pronounced decrease in PC counts of all different IgH-isotypes and subclasses (P≤0.001) together with overall increased IgM (P=0.001) and IgD (P<0.001) plasma levels. Of note, different immune profiles were found per diagnostic subtype of the disease with progressively greater counts in blood of immature B-lymphocytes together with decreased IgMD+, IgG2+, IgA1+ and IgA2+ MBC (P≤0.032) and elevated IgM (P=0.017) plasma levels in ASM cases, increased IgM (P=0.001) and IgD (P=0.001) plasma levels in ISM patients and exacerbated IgE (P<0.001) with decreased IgG (P=0.008) plasma levels in BMM cases.CONCLUSIONOur results reveal a significant dysregulation of the B-cell and PC compartments in blood of SM patients, consistent with distinctly altered antibody-isotype profiles in plasma of BMM vs ISM vs ASM patients.","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"6 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142451421","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":"A partial loss-of-function variant in STAT6 protects against T2 asthma.","authors":"Katla Kristjansdottir,Guðmundur L Norddahl,Erna V Ivarsdottir,Gisli H Halldorsson,Gudmundur Einarsson,Kristbjörg Bjarnadóttir,Gudrun Rutsdottir,Asgeir O Arnthorsson,Christian Erikstrup,Steinunn Gudmundsdottir,Kristbjorg Gunnarsdottir,María I Gunnbjornsdottir,Bjarni V Halldorsson,Hilma Holm,Dora Ludviksdottir,Bjorn R Ludviksson,Søren Brunak,Mie Topholm Bruun,Christina Mikkelsen,Susan Mikkelsen,Bitten Aagaard Jensen,Erik Sørensen,Simon Francis Thomsen,Henrik Ullum,Isleifur Olafsson,Pall T Onundarson,Sisse Rye Ostrowski,Saedis Saevarsdottir,Olof Sigurdardottir,Bardur Sigurgeirsson,Audunn S Snaebjarnarson,Gardar Sveinbjornsson,Gudny E Thorlacius,Gudmar Thorleifsson,Vinicius Tragante,Brynjar Vidarsson,Celeste Porsbjerg,Unnur S Bjornsdottir,Patrick Sulem,Daniel F Gudbjartsson,Pall Melsted,Ole Bv Pedersen,Ingileif Jonsdóttir,Thorunn A Olafsdottir,Kari Stefansson","doi":"10.1016/j.jaci.2024.10.002","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.10.002","url":null,"abstract":"BACKGROUNDSignal Transducer and Activator of Transcription 6 (STAT6) is central to Type 2 (T2) inflammation and common non-coding variants at the STAT6 locus associate with various T2 inflammatory traits, including diseases, and its pathway is widely targeted in asthma treatment.OBJECTIVETo test the association of a rare missense variant in STAT6, p.L406P, with T2 inflammatory traits, including the risk of asthma and allergic diseases, and to characterize its functional consequences in cell culture.METHODSWe tested association of p.L406P with plasma protein levels, white blood cell counts and the risk of asthma and allergic phenotypes. We tested significant associations in other cohorts using a burden test. The effects of p.L406P on STAT6 protein function were examined in cell lines and by comparing CD4+ T-cell responses from carriers and non-carriers of the variant.RESULTSp.L406P associated with reduced plasma levels of STAT6 and IgE as well as with lower eosinophil and basophil counts in blood. It also protected against asthma, mostly driven by severe T2 high asthma. We showed that p.L406P led to lower IL-4-induced activation in luciferase reporter assays and lower levels of STAT6 in CD4+ T cells. We identified multiple genes with expression that was affected by the p.L406P genotype upon IL-4 treatment of CD4+ T cells; the effect was consistent with a weaker IL-4 response in carriers than non-carriers of p.L406P.CONCLUSIONSWe report a partial loss-of-function variant in STAT6, resulting in dampened IL-4 responses and protection from T2 high asthma, implicating STAT6 as an attractive therapeutic target.","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"103 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142451420","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":"Role of DOCK8 in Cytokine Storm Syndromes.","authors":"Mingce Zhang,Remy R Cron,Niansheng Chu,Junior Nguyen,Scott M Gordon,Esraa M Eloseily,T Prescott Atkinson,Peter Weiser,Mark R Walter,Portia A Kreiger,Scott W Canna,Edward M Behrens,Randy Q Cron","doi":"10.1016/j.jaci.2024.10.004","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.10.004","url":null,"abstract":"BACKGROUNDCytokine storm syndromes (CSS), including hemophagocytic lymphohistiocytosis (HLH), are increasingly recognized as hyperinflammatory states leading to multi-organ failure and death. Familial HLH (FHL) in infancy results from homozygous genetic defects in perforin-mediated cytolysis by CD8 T-lymphocytes and natural killer (NK) cells. Later onset CSS are frequently associated with heterozygous defects in FHL genes, but genetic etiologies for most are unknown. We identified rare DOCK8 variants in CSS patients.OBJECTIVEWe explore the role of CSS patient-derived DOCK8 mutations on cytolytic activity in NK cells. We further study effects of DOCK8 deficiency in murine models of CSS.METHODSDOCK8 cDNA from 2 unrelated CSS patients with different missense mutations were introduced into human NK-92 NK cells by foamy virus transduction. NK cell degranulation (CD107a), cytolytic activity against K562 target cells, and interferon-gamma (IFNγ) production were explored by flow cytometry. A third CSS patient DOCK8 mRNA splice acceptor site variant was explored by exon trapping. Dock8-/- mice were assessed for features of CSS (weight loss, splenomegaly, hepatic inflammation, cytopenias, and IFNγ levels) upon challenge with lymphocytic choriomeningitis virus (LCMV) and excess IL-18.RESULTSBoth patient DOCK8 missense mutations decreased cytolytic function in NK cells in a partial dominant-negative fashion in vitro. The patient DOCK8 splice variant disrupted mRNA splicing in vitro. LCMV infection promoted CSS in Dock8-/- mice and interacted with excess IL-18 limiting T-cell numbers while promoting CD8 T-cell hyperactivation.CONCLUSIONMutations in DOCK8 may contribute to CSS-like hyperinflammatory states by altering cytolytic function in a threshold model of disease.","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":"31 1","pages":""},"PeriodicalIF":14.2,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142451422","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":"Omics in allergy and asthma.","authors":"Hirohisa Saito, Masato Tamari, Kenichiro Motomura, Masashi Ikutani, Susumu Nakae, Kenji Matsumoto, Hideaki Morita","doi":"10.1016/j.jaci.2024.09.023","DOIUrl":"10.1016/j.jaci.2024.09.023","url":null,"abstract":"<p><p>This review explores the transformative impact of omics technologies on allergy and asthma research in recent years, focusing on advancements in high-throughput technologies related to genomics and transcriptomics. In particular, the rapid spread of single-cell RNA sequencing has markedly advanced our understanding of the molecular pathology of allergic diseases. Furthermore, high-throughput genome sequencing has accelerated the discovery of monogenic disorders that were previously overlooked as ordinary intractable allergic diseases. We also introduce microbiomics, proteomics, lipidomics, and metabolomics, which are quickly growing areas of research interest, although many of their current findings remain inconclusive as solid evidence. By integrating these omics data, we will gain deeper insights into disease mechanisms, leading to the development of precision medicine approaches that promise to enhance treatment outcomes.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390675","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":"IL-4 and dendritic cells in atopic dermatitis: Old dogs learn new tricks.","authors":"Donata Vercelli","doi":"10.1016/j.jaci.2024.10.001","DOIUrl":"10.1016/j.jaci.2024.10.001","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400313","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 rs6967330 minor allele in CDHR3 is a significant risk factor for severe acute exacerbations in chronic rhinosinusitis.","authors":"Sunny Palumbo, Joseph Irish, Nirushan Narendran, Debra A Stern, Sophia Volpe, Christopher H Le, Rebekah Starks, Anthony Bosco, Fernando D Martinez, Eugene H Chang","doi":"10.1016/j.jaci.2024.09.025","DOIUrl":"10.1016/j.jaci.2024.09.025","url":null,"abstract":"<p><strong>Background: </strong>Acute exacerbations of chronic rhinosinusitis (AECRS) are commonly triggered by rhinovirus (RV) infections with secondary bacterial infections. Risk factors for AECRS are not well understood.</p><p><strong>Objective: </strong>We sought to determine whether carriers of the minor allele rs6967330 (AA/AG) in the cadherin-related family member 3 (CDHR3) gene have an increased risk for RV infections in AECRS in vivo and identify CDHR3 genotype-dependent host responses to RV infection in differentiated nasal airway-liquid interface (ALI) cultures ex vivo.</p><p><strong>Methods: </strong>We performed a prospective year-long study of adult subjects with chronic rhinosinusitis by the rs6967330 genotype (AA/AG, n = 16; GG, n = 38). We contacted subjects every 2 weeks, and if they reported AECRS, then clinical data were collected. ALI cultures of adults with chronic rhinosinusitis (AG/AA, n = 19; GG, n = 19) were challenged with RV-A and RV-C. We measured viral copy numbers at 4 and 48 hours postinfection and RNA transcriptomes and cytokines at 48 hours postinfection.</p><p><strong>Results: </strong>Subjects with the minor allele had significantly higher rates of RV and bacterial infections than those with the major allele. ALI minor allele cultures had higher viral copy numbers of RV-A and RV-C after 48 hours compared with the major allele. Differentially expressed genes and pathways identified an upregulation of IL-10 and IL-4/IL-13 pathways and a significant downregulation of Toll-like receptor pathways in the minor allele cultures after RV-A and RV-C infection. Unsupervised hierarchical analysis of all differentially expressed genes suggested that allergic rhinitis had an additive effect on this response.</p><p><strong>Conclusions: </strong>The rs6967330 minor allele is associated with increased RV-A and RV-C replication, downregulation of Toll-like receptor-mediated responses, and increased type-2 and cytokine and chemokine responses during RV infection.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400314","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":"Differential Tfh cell phenotypes distinguish IgE-mediated milk allergy from eosinophilic esophagitis in children.","authors":"Daniel Lozano-Ojalvo, Xin Chen, Wajiha Kazmi, David Menchén-Martínez, Leticia Pérez-Rodríguez, Weslley Fernandes-Braga, Scott Tyler, Keith Benkov, Nanci Pittman, Joanne Lai, Hugh A Sampson, Maria Curotto de Lafaille, David Dunkin, M Cecilia Berin","doi":"10.1016/j.jaci.2024.09.024","DOIUrl":"https://doi.org/10.1016/j.jaci.2024.09.024","url":null,"abstract":"<p><strong>Background: </strong>IgE-mediated food allergy and eosinophilic esophagitis (EoE) are diseases commonly triggered by milk. Milk-responsive CD4⁺ T cells producing type 2 cytokines are present in both diseases, yet the clinical manifestation of disease in milk allergy (MA) and EoE are distinct.</p><p><strong>Objective: </strong>To identify CD4⁺ T cell differences between EoE and MA that may be responsible for distinct disease manifestations.</p><p><strong>Methods: </strong>The total and milk-specific CD4⁺ T cell phenotype of children with milk allergy (MA), EoE (active or in remission) and controls was measured using spectral flow cytometry of peripheral blood (all groups) or esophageal biopsies (EoE and control).</p><p><strong>Results: </strong>Circulating milk-responsive T cells could be identified in active (A)-EoE and MA. An increased frequency of Th2A cells was also noted in MA and EoE. In circulating T cells, type 2 cytokine production was elevated in MA, but not EoE. Within the milk-responsive Tfh subset, a dichotomy of phenotype was noted: Tfh13 cells predominated in MA, while IL-10-producing Tfh cells predominated in EoE. In the esophagus, CD4⁺ T cells were constitutively activated and expressed not only type 2 cytokines, but also IL-10 and IL-21 in A-EoE. There was production of IgG4 from CD38⁺ plasma cells in close proximity to CD4⁺ T cells. In vitro activation studies demonstrated that IL-10 and IL-21 elicited strong IgG4 responses in B lymphocytes, while IL-4 and IL-13 promoted IgE production.</p><p><strong>Conclusion: </strong>Our studies demonstrate a dichotomy of Tfh responses that may be the basis for the different clinical manifestations to milk in EoE and MA.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400312","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":"JAK-STAT signaling pathway, immunodeficiency, inflammation, immune dysregulation, and inborn errors of immunity.","authors":"Simran Samra, Jenna R E Bergerson, Alexandra F Freeman, Stuart E Turvey","doi":"10.1016/j.jaci.2024.09.020","DOIUrl":"10.1016/j.jaci.2024.09.020","url":null,"abstract":"<p><p>The Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling cascade is an evolutionarily conserved signal transduction pathway that regulates many vital cellular processes, including immune function and hematopoiesis. Human genetic variants that disrupt JAK-STAT signaling are being found to cause a rapidly increasing number of diseases, including both germline-encoded inborn errors of immunity (IEI) and acquired somatic variants, causing a so-called phenocopy of the IEI. Multiple genetic mechanisms are responsible for this growing group of JAK-STAT diseases including loss-of-function, gain-of-function, and dominant negative effects. In this review, we discuss the clinical presentation and pathogenesis of all currently described JAK-STAT defects, as well as provide an overview of the guiding principles to consider in diagnosing and treating these conditions.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380907","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}