Journal of Allergy and Clinical Immunology最新文献

{"title":"Ruxolitinib treatment ameliorates clinical, immunologic, and transcriptomic aberrations in patients with STAT3 gain-of-function disease.","authors":"Feyza Bayram Catak, Mehmet Cihangir Catak, Royala Babayeva, John Toubia, Nicholas I Warnock, Fatih Celmeli, Demet Hafizoglu, Nalan Yakici, Basak Kayaoglu, Naz Surucu, Ezgi Yalcin Gungoren, Salim Can, Melek Yorgun Altunbas, Ibrahim Serhat Karakus, Ayca Kiykim, Fazil Orhan, Sevgi Bilgic Eltan, Elif Karakoc-Aydiner, Ahmet Ozen, Baran Erman, Mayda Gursel, Chung Hoow Kok, Gökhan Cildir, Safa Baris","doi":"10.1016/j.jaci.2024.11.032","DOIUrl":"10.1016/j.jaci.2024.11.032","url":null,"abstract":"<p><strong>Background: </strong>Signal transducer and activator of transcription 3 (STAT3) gain-of-function (GOF) disease presents with lymphoproliferation, autoimmunity, and failure to thrive. Although Janus kinase inhibitors have alleviated symptoms, their effects on disease pathogenesis remain unclear.</p><p><strong>Objective: </strong>We prospectively investigated the clinical, immunologic, and transcriptomic responses of 4 patients with STAT3 GOF under long-term ruxolitinib treatment.</p><p><strong>Methods: </strong>We conducted clinical and immunologic evaluations at baseline and after ruxolitinib treatment at 3, 8, 12, and more than 12 months. Our assessments included measurement of levels of circulating T follicular helper cells, regulatory T cells, and cytokines, as well as proliferation assays. Furthermore, we investigated the transcriptomic changes with treatment and conducted T-cell receptor sequencing.</p><p><strong>Results: </strong>Ruxolitinib achieved substantial control over the clinical manifestations. Posttreatment evaluations demonstrated a notable increase in naive CD4⁺ and CD8⁺ T-cell populations, alongside a significant reduction in effector memory T-cell levels. Additionally, there was a decrease in levels of circulating T follicular helper cells and double-negative T cells. Regulatory T-cell percentages and their canonical markers, which were already reduced before treatment, declined further with ruxolitinib. The treatment did not alter the production of IL-4, IL-17A, IL-10, and IFN-γ cytokines by the CD4⁺ T cells. Importantly, ruxolitinib effectively normalized the previously dysregulated transcriptome profile in PBMCs, bringing it closer to that of healthy controls. This normalization was most striking in the downregulation of STAT3-targeted genes, interferon-related genes, myeloid cell activation, and cytotoxic effector CD8⁺ T-cell genes, with effects persisting for up to 12 months. Self-reactive T-cell indices based on T-cell receptor repertoire analysis revealed potential autoreactive cell clones in the patient samples.</p><p><strong>Conclusion: </strong>Ruxolitinib reversed cellular and transcriptomic signatures, enhancing our understanding of the disease's pathophysiology and highlighting essential immunologic markers for precise monitoring.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780275","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":"Atopic dermatitis, food allergy, anaphylaxis, and other atopic conditions.","authors":"Michelle L Hernandez, Pedro Giavina Bianchi, Richard Lockey, Sarita U Patil","doi":"10.1016/j.jaci.2024.10.011","DOIUrl":"10.1016/j.jaci.2024.10.011","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":"1416-1418"},"PeriodicalIF":11.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466076","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":"Interactions between eosinophils and IL-5Rα-positive mast cells in nonadvanced systemic mastocytosis.","authors":"Guillaume Lefèvre, Jean-Baptiste Gibier, Antonino Bongiovanni, Ludovic Lhermitte, Julien Rossignol, Emilie Anglo, Arnaud Dendooven, Romain Dubois, Louis Terriou, David Launay, Stéphane Barete, Stéphane Esnault, Laurent Frenzel, Clément Gourguechon, Thomas Ballul, Frédéric Dezoteux, Delphine Staumont-Salle, Marie-Christine Copin, Rachel Rignault-Bricard, Thiago Trovati Maciel, Gandhi Damaj, Meryem Tardivel, Marie Crinquette-Verhasselt, Patrice Dubreuil, Leila Maouche-Chrétien, Julie Bruneau, Olivier Lortholary, Nicolas Duployez, Hélène Behal, Thierry Jo Molina, Olivier Hermine","doi":"10.1016/j.jaci.2024.07.025","DOIUrl":"10.1016/j.jaci.2024.07.025","url":null,"abstract":"<p><strong>Background: </strong>Bidirectional interactions between eosinophils and mast cells (MCs) have been reported in various allergic diseases. Bone marrow (BM) eosinophilia, and to a lesser extent blood eosinophilia, is common in systemic mastocytosis (SM), but its significance remains unknown.</p><p><strong>Objective: </strong>We described blood and BM eosinophil characteristics in SM.</p><p><strong>Methods: </strong>A large collection of BM biopsy samples was analyzed using immunohistochemical staining and whole-slide imaging. Eosinophil and extracellular granules were detected by eosinophil peroxidase (EPX) staining and MCs by KIT staining. Complementary analyses were conducted using flow cytometry and immunofluorescence.</p><p><strong>Results: </strong>Eosinophil infiltrates and large areas of eosinophil degranulation were observed within or around BM MC infiltrates in SM. EPX staining surface, highlighting intact eosinophils and eosinophil degranulation, was higher in nonadvanced SM (n = 37 BM biopsy samples) compared with both controls (n = 8, P = .0003) and advanced SM (n = 24, P = .014). In nonadvanced SM, positive correlations were observed between serum tryptase levels and percentages of eosinophil counts in BM aspirations (Spearman r coefficient r = 0.38, P = .038), eosinophils count in BM biopsy samples (r = 0.45, P = .007), EPX staining (r = 0.37, P = .035), and eosinophil degranulation (r = 0.39, P = .023). Eosinophil counts in BM biopsy samples also correlated with MC counts (r = 0.47, P = .006) and KIT staining surface (r = 0.49, P = .003). BM MCs expressed IL-5 receptor and other usual eosinophil cytokine/chemokine receptors, and blood eosinophils displayed several increased surface markers compared with controls, suggesting an activated state.</p><p><strong>Conclusion: </strong>Our data suggest possible cross talk between MCs and eosinophils, supporting MC tryptase release and MC activation-related symptoms. This suggests a rationale for targeting eosinophils in nonadvanced SM not fully controlled by other therapies.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":"1523-1533"},"PeriodicalIF":11.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995785","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":"Subcutaneous immunotherapy for bee venom allergy induces epitope spreading and immunophenotypic changes in allergen-specific memory B cells.","authors":"Craig I McKenzie, Simone Reinwald, Brett Averso, Brett Spurrier, Andrew Satz, Anouk von Borstel, Sabina Masinovic, Nirupama Varese, Pei Mun Aui, Bruce D Wines, P Mark Hogarth, Mark Hew, Jennifer M Rolland, Robyn E O'Hehir, Menno C van Zelm","doi":"10.1016/j.jaci.2024.08.019","DOIUrl":"10.1016/j.jaci.2024.08.019","url":null,"abstract":"<p><strong>Background: </strong>Allergen immunotherapy (AIT) is the only disease-modifying treatment for allergic disorders. We have recently discovered that allergen-specific memory B cells (Bmem) are phenotypically altered after 4 months of sublingual AIT for ryegrass pollen allergy. Whether these effects are shared with subcutaneous allergen immunotherapy (SCIT) and affect the epitope specificity of Bmem remain unknown.</p><p><strong>Objective: </strong>The study aimed to evaluate the phenotype and antigen receptor sequences of Bmem specific to the major bee venom (BV) allergen Api m 1 before and after ultra-rush SCIT for BV allergy.</p><p><strong>Methods: </strong>Recombinant Api m 1 protein tetramers were generated to evaluate basophil activation in a cohort of individuals with BV allergy before and after BV SCIT. Comprehensive flow cytometry was performed to evaluate and purify Api m 1-specific Bmem. Immunoglobulin genes from single Api m 1-specific Bmem were sequenced and structurally modeled onto Api m 1.</p><p><strong>Results: </strong>SCIT promoted class switching of Api m 1-specific Bmem to IgG₂ and IgG₄ with increased expression of CD23 and CD29. Furthermore, modeling of Api m 1-specific immunoglobulin from Bmem identified a suite of possible new and diverse allergen epitopes on Api m 1 and highlighted epitopes that may preferentially be bound by immunoglobulin after SCIT.</p><p><strong>Conclusions: </strong>AIT induces shifting of epitope specificity and phenotypic changes in allergen-specific Bmem.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":"1511-1522"},"PeriodicalIF":11.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142107711","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":"Obesity and hormonal influences on asthma: Mechanisms, management challenges, and emerging therapeutic strategies.","authors":"Natalia Weare-Regales, Tara Carr, Fernando Holguin, Christopher Andrew Tibbitt, Richard F Lockey","doi":"10.1016/j.jaci.2024.09.018","DOIUrl":"10.1016/j.jaci.2024.09.018","url":null,"abstract":"<p><p>Obesity and hormone dysregulation, common comorbidities of asthma, not only influence asthma risk and onset but can also complicate its management. The pathobiologic characteristics of obesity, such as insulin resistance and metabolism alterations, can impact lung function and airway inflammation while highlighting potential opportunities for therapeutic intervention. Likewise, obesity alters immune cell phenotypes and corticosteroid pharmacokinetics. Hormones such as sex hormones, incretins, and thyroid hormones can also affect asthma. This review highlights the mechanisms underlying obesity-related asthma and hormonal pathologies while exploring potential therapeutic strategies and the need for more research and innovative approaches in managing these comorbid conditions.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":"1355-1368"},"PeriodicalIF":11.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371936","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":"PLCG2 variants in cherubism.","authors":"Jennifer G Chester, Benjamin Carcamo, David A Gudis, Daniel Bustamante, Sidney B Eisig, Michael J Ombrello, Wendy K Chung, Joshua D Milner","doi":"10.1016/j.jaci.2024.08.016","DOIUrl":"10.1016/j.jaci.2024.08.016","url":null,"abstract":"<p><strong>Background: </strong>Cherubism is most commonly caused by rare heterozygous gain-of-function (GOF) missense variants in SH3BP2, which appear to signal through phospholipase C gamma 2 (PLCG2) to cause excessive osteoclast activity leading to expansile lesions in facial bones in childhood. GOF variants in PLCG2 lead to autoinflammatory PLCG2-associated antibody deficiency and immune dysregulation (autoinflammatory PLAID, or PLAID-GOF), characterized by variably penetrant autoinflammatory, autoimmune, infectious, and atopic manifestations. Cherubism has not been reported in PLAID to date.</p><p><strong>Objective: </strong>We determined whether GOF PLCG2 variants may be associated with cherubism.</p><p><strong>Methods: </strong>Clinical, laboratory, and genomic data from 2 patients with cherubism and other clinical symptoms observed in patients with PLCG2 variants were reviewed. Primary B-cell receptor-induced calcium flux was assessed by flow cytometry.</p><p><strong>Results: </strong>Two patients with lesions consistent with cherubism but no SH3BP2 variants were found to have rare PLCG2 variants previously shown to be GOF in vitro, leading to increased primary B-cell receptor-induced calcium flux in one patient's B cells. Variable humoral defects, autoinflammatory rash, and other clinical and laboratory findings consistent with PLAID were observed as well.</p><p><strong>Conclusion: </strong>GOF PLCG2 variants likely represent a novel genetic driver of cherubism and should be assessed in SH3BP2-negative cases. Expansile bony lesions expand the phenotypic landscape of autoinflammatory PLAID, and bone imaging should be considered in PLAID patients.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":"1554-1558"},"PeriodicalIF":11.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142093180","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":"1378-1390"},"PeriodicalIF":11.4,"publicationDate":"2024-12-01","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":"Reply.","authors":"Sizheng Steven Zhao","doi":"10.1016/j.jaci.2024.09.003","DOIUrl":"10.1016/j.jaci.2024.09.003","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":"1559-1560"},"PeriodicalIF":11.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347125","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":"Defining the overlap between asthma and bronchiectasis: A call for consensus definition.","authors":"Sang Hyuk Kim, Bumhee Yang, Kyung Hoon Min, Hyun Lee","doi":"10.1016/j.jaci.2024.05.033","DOIUrl":"10.1016/j.jaci.2024.05.033","url":null,"abstract":"","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":"1560-1561"},"PeriodicalIF":11.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466077","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":"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 more than 20 years ago, emphasizing the connection between asthma and upper airway comorbidities (UACs) such as allergic or nonallergic rhinitis, chronic rhinosinusitis with or without nasal polyps, and aspirin/nonsteroidal anti-inflammatory drug-exacerbated respiratory disease. Since then, numerous studies have demonstrated that UACs are closely related and affect asthma phenotypes. Recognizing these UACs and managing them 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 better quality of life. Moreover, it is important to explore the field of respiratory biologics, which represents the latest advancements in medical treatment options for patients with asthma and UACs.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":" ","pages":"1343-1354"},"PeriodicalIF":11.4,"publicationDate":"2024-12-01","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}