{"title":"membroinitre病的免疫学异质性:CD4+ T细胞亚群分析揭示了三种不同的免疫表型","authors":"Huaili Jiang , Yanxia Zhan , Menglong Zhao , Shujie Zhang , Lei Zhou , Kanglun Jiang , Yunfeng Cheng , Xinsheng Huang , Xiaofeng Xie","doi":"10.1016/j.jneuroim.2025.578743","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Ménière's disease (MD) remains a heterogeneous disorder with unclear pathogenesis. While immune dysregulation has been implicated, the specific role of CD4+ T cell subsets and their clinical correlations in MD are poorly understood.</div></div><div><h3>Methods</h3><div>We performed comprehensive immune profiling of 30 MD patients and 27 healthy controls using flow cytometry to analyze six CD4+ T cell subsets (Th1, Th2, Th17, Treg, TGF-β+, TNF-α+) and multiplex cytokine analysis of 16 inflammatory mediators plus IgE. Unsupervised hierarchical clustering identified distinct immune phenotypes, and cox regression analysis determined biomarkers of disease activity.</div></div><div><h3>Results</h3><div>Three distinct immunophenotypes were identified: Autoinflammatory (35.7 %, elevated Th1/TNF-α + cells), inactive (28.6 %, balanced profiles), and type 2-skewed (35.7 %, increased Treg/TGF-β + cells). MD patients showed significantly altered Th1/Th2/Th17 balance with elevated TGF-β + cells (<em>p</em> < 0.001) and decreased serum IFN-γ, IL-1β, and IL-17 a levels, while CCL3/CCL4 chemokines were increased. Cluster-specific immune-clinical correlations revealed distinct pathophysiological patterns. IL-2Rα (HR = 0.18, <em>p</em> = 0.007) and IFN-γ (HR = 0.26, <em>p</em> = 0.046) may represent biomarkers of disease activity.</div></div><div><h3>Conclusion</h3><div>MD exhibits significant immunological heterogeneity with three distinct CD4+ T cell-defined phenotypes. These findings support the development of personalized treatment approaches and suggest potential biomarkers of disease activity, advancing our understanding of MD pathogenesis through comprehensive immune profiling</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"409 ","pages":"Article 578743"},"PeriodicalIF":2.5000,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Immunological heterogeneity in Ménière's disease: CD4+ T cell subset profiling reveals three distinct Immunophenotypes\",\"authors\":\"Huaili Jiang , Yanxia Zhan , Menglong Zhao , Shujie Zhang , Lei Zhou , Kanglun Jiang , Yunfeng Cheng , Xinsheng Huang , Xiaofeng Xie\",\"doi\":\"10.1016/j.jneuroim.2025.578743\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>Ménière's disease (MD) remains a heterogeneous disorder with unclear pathogenesis. While immune dysregulation has been implicated, the specific role of CD4+ T cell subsets and their clinical correlations in MD are poorly understood.</div></div><div><h3>Methods</h3><div>We performed comprehensive immune profiling of 30 MD patients and 27 healthy controls using flow cytometry to analyze six CD4+ T cell subsets (Th1, Th2, Th17, Treg, TGF-β+, TNF-α+) and multiplex cytokine analysis of 16 inflammatory mediators plus IgE. Unsupervised hierarchical clustering identified distinct immune phenotypes, and cox regression analysis determined biomarkers of disease activity.</div></div><div><h3>Results</h3><div>Three distinct immunophenotypes were identified: Autoinflammatory (35.7 %, elevated Th1/TNF-α + cells), inactive (28.6 %, balanced profiles), and type 2-skewed (35.7 %, increased Treg/TGF-β + cells). MD patients showed significantly altered Th1/Th2/Th17 balance with elevated TGF-β + cells (<em>p</em> < 0.001) and decreased serum IFN-γ, IL-1β, and IL-17 a levels, while CCL3/CCL4 chemokines were increased. Cluster-specific immune-clinical correlations revealed distinct pathophysiological patterns. IL-2Rα (HR = 0.18, <em>p</em> = 0.007) and IFN-γ (HR = 0.26, <em>p</em> = 0.046) may represent biomarkers of disease activity.</div></div><div><h3>Conclusion</h3><div>MD exhibits significant immunological heterogeneity with three distinct CD4+ T cell-defined phenotypes. These findings support the development of personalized treatment approaches and suggest potential biomarkers of disease activity, advancing our understanding of MD pathogenesis through comprehensive immune profiling</div></div>\",\"PeriodicalId\":16671,\"journal\":{\"name\":\"Journal of neuroimmunology\",\"volume\":\"409 \",\"pages\":\"Article 578743\"},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2025-09-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of neuroimmunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0165572825002243\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of neuroimmunology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0165572825002243","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Immunological heterogeneity in Ménière's disease: CD4+ T cell subset profiling reveals three distinct Immunophenotypes
Background
Ménière's disease (MD) remains a heterogeneous disorder with unclear pathogenesis. While immune dysregulation has been implicated, the specific role of CD4+ T cell subsets and their clinical correlations in MD are poorly understood.
Methods
We performed comprehensive immune profiling of 30 MD patients and 27 healthy controls using flow cytometry to analyze six CD4+ T cell subsets (Th1, Th2, Th17, Treg, TGF-β+, TNF-α+) and multiplex cytokine analysis of 16 inflammatory mediators plus IgE. Unsupervised hierarchical clustering identified distinct immune phenotypes, and cox regression analysis determined biomarkers of disease activity.
Results
Three distinct immunophenotypes were identified: Autoinflammatory (35.7 %, elevated Th1/TNF-α + cells), inactive (28.6 %, balanced profiles), and type 2-skewed (35.7 %, increased Treg/TGF-β + cells). MD patients showed significantly altered Th1/Th2/Th17 balance with elevated TGF-β + cells (p < 0.001) and decreased serum IFN-γ, IL-1β, and IL-17 a levels, while CCL3/CCL4 chemokines were increased. Cluster-specific immune-clinical correlations revealed distinct pathophysiological patterns. IL-2Rα (HR = 0.18, p = 0.007) and IFN-γ (HR = 0.26, p = 0.046) may represent biomarkers of disease activity.
Conclusion
MD exhibits significant immunological heterogeneity with three distinct CD4+ T cell-defined phenotypes. These findings support the development of personalized treatment approaches and suggest potential biomarkers of disease activity, advancing our understanding of MD pathogenesis through comprehensive immune profiling
期刊介绍:
The Journal of Neuroimmunology affords a forum for the publication of works applying immunologic methodology to the furtherance of the neurological sciences. Studies on all branches of the neurosciences, particularly fundamental and applied neurobiology, neurology, neuropathology, neurochemistry, neurovirology, neuroendocrinology, neuromuscular research, neuropharmacology and psychology, which involve either immunologic methodology (e.g. immunocytochemistry) or fundamental immunology (e.g. antibody and lymphocyte assays), are considered for publication.