Age-Stratified Immune Characteristics in Central Nervous System Tuberculosis Patients: A Comparative T lymphocyte Subset Analysis within a Cohort of 862 Extrapulmonary Tuberculosis Patients

Age-Stratified Immune Characteristics in Central Nervous System Tuberculosis Patients: A Comparative T lymphocyte Subset Analysis within a Cohort of 862 Extrapulmonary Tuberculosis Patients | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Age-Stratified Immune Characteristics in Central Nervous System Tuberculosis Patients: A Comparative T lymphocyte Subset Analysis within a Cohort of 862 Extrapulmonary Tuberculosis Patients Muxing Chen, Fan Zhang, Yiping Liu, Youfei Lin, Di Wu, Xiaohong Chen This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7519458/v2 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 05 Dec, 2025 Read the published version in BMC Infectious Diseases → Version 2 posted 9 You are reading this latest preprint version Show more versions Abstract Background: Central nervous system tuberculosis (CNS-TB) remains a critical clinical challenge with high mortality, and its underlying immunopathological mechanisms have not been fully elucidated. This study aimed to investigate age-dependent variations in T lymphocyte subsets among CNS-TB patients and their clinical implications. Methods: In this retrospective study, we analysed 862 patients with extrapulmonary tuberculosis (EPTB) admitted to Fuzhou Pulmonary Hospital between April 2018 and April 2024. The cohort comprised 177 CNS-TB patients and a control group of 685 non-central nervous system extrapulmonary tuberculosis (non-CNS EPTB) patients. We comprehensively compared demographic characteristics, medical history, nutritional parameters, T lymphocyte subsets (CD3+, CD4+, CD8+, and CD45+), and neutrophil-to-lymphocyte ratio (NLR) between groups, with detailed age stratification and correlation analyses. Results: Baseline characteristics, medical history, and nutritional parameters were not significantly different between the groups. CNS-TB patients exhibited markedly reduced T lymphocyte counts, which were most pronounced in the 25–54 year age group (CD3+: 735.5 vs 1010.0 cells/μL, P<0.001; CD4+: 389.0 vs 576.0 cells/μL, P<0.001; CD8+: 285.5 vs 358.0 cells/μL, P=0.013; and CD45+: 1109.5 vs 1448.0 cells/μL, P<0.001). These differences persisted but attenuated in the 55–64 years age group, with no significant disparities in the 18–24 and ≥65 years age groups. Age-stratified analysis revealed a progressive NLR increase, peaking in patients ≥65 years (7.07 vs 4.67, P=0.010), with diminishing intergroup differences. Correlation analysis revealed strong positive correlations among T-lymphocyte subsets (r=0.52--0.96, P<0.001), significant positive correlations with lymphocyte counts (r=0.52--0.71, P<0.001) and moderate negative correlations with the NLR (r=-0.27--0.36, P<0.001). Conclusion: CNS-TB patients display characteristic T lymphocyte depletion and elevated NLRs, with dynamic age-dependent immune characteristics most prominent in immunocompetent adults. Lymphocyte counts can predict T-cell subset levels, whereas NLR values can predict inflammatory and immune response states. This study provides the first comprehensive demonstration of age-dependent immune characteristics in CNS-TB patients, offering a theoretical foundation for age-stratified immune monitoring strategies. Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 05 Dec, 2025 Read the published version in BMC Infectious Diseases → Version 2 posted Editorial decision: Revision requested 24 Oct, 2025 Reviews received at journal 17 Oct, 2025 Reviewers agreed at journal 17 Oct, 2025 Reviews received at journal 23 Jun, 2025 Reviewers agreed at journal 09 Jun, 2025 Reviewers invited by journal 14 May, 2025 Editor assigned by journal 06 May, 2025 Submission checks completed at journal 06 May, 2025 First submitted to journal 06 May, 2025 You are reading this latest preprint version Show more versions Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7519458","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[{"code":1,"date":"2025-09-05 17:33:50","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":513139347,"identity":"8a967b6e-d587-4bb8-aa6c-bca3bf194840","order_by":0,"name":"Muxing Chen","email":"","orcid":"","institution":"Pulmonary Hospital of Fuzhou of Fujian Province","correspondingAuthor":false,"prefix":"","firstName":"Muxing","middleName":"","lastName":"Chen","suffix":""},{"id":513139348,"identity":"cae582b3-f63d-416c-a5a5-ce05d5e0caa1","order_by":1,"name":"Fan Zhang","email":"","orcid":"","institution":"Pulmonary Hospital of Fuzhou of Fujian Province","correspondingAuthor":false,"prefix":"","firstName":"Fan","middleName":"","lastName":"Zhang","suffix":""},{"id":513139349,"identity":"9b895828-d901-4bd2-a304-b03c662795f0","order_by":2,"name":"Yiping Liu","email":"","orcid":"","institution":"Pulmonary Hospital of Fuzhou of Fujian Province","correspondingAuthor":false,"prefix":"","firstName":"Yiping","middleName":"","lastName":"Liu","suffix":""},{"id":513139350,"identity":"639e4114-c4d3-40dd-af01-e3bc280fa71b","order_by":3,"name":"Youfei Lin","email":"","orcid":"","institution":"Pulmonary Hospital of Fuzhou of Fujian Province","correspondingAuthor":false,"prefix":"","firstName":"Youfei","middleName":"","lastName":"Lin","suffix":""},{"id":513139351,"identity":"d3765101-5e08-4904-8a1c-61ded2b62b1a","order_by":4,"name":"Di Wu","email":"","orcid":"","institution":"Pulmonary Hospital of Fuzhou of Fujian Province","correspondingAuthor":false,"prefix":"","firstName":"Di","middleName":"","lastName":"Wu","suffix":""},{"id":513139352,"identity":"3bd0335c-0c02-43fc-978d-7246c470405d","order_by":5,"name":"Xiaohong Chen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA1ElEQVRIiWNgGAWjYFACHhBhI8fP3nzgwIcK4rWkGUv2HEs8OOMM8VoOJW644WN8mLeFCA38M3IPPi74dcBYcgbPhwO8DQzy/GIH8GuROHMu2Xhm3x05funeDQckdzAYzpydgF+LAXuPmTRvzzNjyTlnNxwwPMOQYHCbkBZmHpCWw0C/5Dw4kNhGjBaQLTw/wFoYDhwkRovEmTPGxrwN4EA2ONhwRoKwX/hn5Bg+5vkDjsrHn/9U2MjzSxPQAgaMbQhbiVAOBn+IVTgKRsEoGAUjEgAAwPJMA6tnRnMAAAAASUVORK5CYII=","orcid":"","institution":"Pulmonary Hospital of Fuzhou of Fujian Province","correspondingAuthor":true,"prefix":"","firstName":"Xiaohong","middleName":"","lastName":"Chen","suffix":""}],"badges":[],"createdAt":"2025-09-02 15:44:32","currentVersionCode":2,"declarations":{"humanSubjects":true,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":true,"humanSubjectConsent":true,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-7519458/v2","doiUrl":"https://doi.org/10.21203/rs.3.rs-7519458/v2","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12879-025-12258-7","type":"published","date":"2025-12-05T15:57:42+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":97724066,"identity":"9860faee-7866-4dcf-9dbe-efc8845466e5","added_by":"auto","created_at":"2025-12-08 16:11:32","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":658723,"visible":true,"origin":"","legend":"","description":"","filename":"AgeStratifiedImmuneCharacteristicsinCentralNervousSystemTuberculosisPatientsAComparativeTlymphocyteSubsetAnalysiswithinaCohortof862ExtrapulmonaryTuberculosisPatients..pdf","url":"https://assets-eu.researchsquare.com/files/rs-7519458/v2_covered_6ef698ae-fec0-40ce-8c57-0832215edef2.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Age-Stratified Immune Characteristics in Central Nervous System Tuberculosis Patients: A Comparative T lymphocyte Subset Analysis within a Cohort of 862 Extrapulmonary Tuberculosis Patients","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"Fuzhou Pulmonary Hospital of Fujian","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-7519458/v2","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7519458/v2","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Background: Central nervous system tuberculosis (CNS-TB) remains a critical clinical challenge with high mortality, and its underlying immunopathological mechanisms have not been fully elucidated. This study aimed to investigate age-dependent variations in T lymphocyte subsets among CNS-TB patients and their clinical implications.\nMethods: In this retrospective study, we analysed 862 patients with extrapulmonary tuberculosis (EPTB) admitted to Fuzhou Pulmonary Hospital between April 2018 and April 2024. The cohort comprised 177 CNS-TB patients and a control group of 685 non-central nervous system extrapulmonary tuberculosis (non-CNS EPTB) patients. We comprehensively compared demographic characteristics, medical history, nutritional parameters, T lymphocyte subsets (CD3+, CD4+, CD8+, and CD45+), and neutrophil-to-lymphocyte ratio (NLR) between groups, with detailed age stratification and correlation analyses.\nResults: Baseline characteristics, medical history, and nutritional parameters were not significantly different between the groups. CNS-TB patients exhibited markedly reduced T lymphocyte counts, which were most pronounced in the 25–54 year age group (CD3+: 735.5 vs 1010.0 cells/μL, P\u003c0.001; CD4+: 389.0 vs 576.0 cells/μL, P\u003c0.001; CD8+: 285.5 vs 358.0 cells/μL, P=0.013; and CD45+: 1109.5 vs 1448.0 cells/μL, P\u003c0.001). These differences persisted but attenuated in the 55–64 years age group, with no significant disparities in the 18–24 and ≥65 years age groups. Age-stratified analysis revealed a progressive NLR increase, peaking in patients ≥65 years (7.07 vs 4.67, P=0.010), with diminishing intergroup differences. Correlation analysis revealed strong positive correlations among T-lymphocyte subsets (r=0.52--0.96, P\u003c0.001), significant positive correlations with lymphocyte counts (r=0.52--0.71, P\u003c0.001) and moderate negative correlations with the NLR (r=-0.27--0.36, P\u003c0.001).\nConclusion: CNS-TB patients display characteristic T lymphocyte depletion and elevated NLRs, with dynamic age-dependent immune characteristics most prominent in immunocompetent adults. Lymphocyte counts can predict T-cell subset levels, whereas NLR values can predict inflammatory and immune response states. This study provides the first comprehensive demonstration of age-dependent immune characteristics in CNS-TB patients, offering a theoretical foundation for age-stratified immune monitoring strategies.","manuscriptTitle":"Age-Stratified Immune Characteristics in Central Nervous System Tuberculosis Patients: A Comparative T lymphocyte Subset Analysis within a Cohort of 862 Extrapulmonary Tuberculosis Patients","msid":"","msnumber":"","nonDraftVersions":[{"code":2,"date":"2025-09-10 13:44:25","doi":"10.21203/rs.3.rs-7519458/v2","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-10-24T06:54:17+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-17T15:48:48+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"283209442718838484537189184555745008640","date":"2025-10-17T10:17:28+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-06-23T18:07:53+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"42951562348800263387773017476901330487","date":"2025-06-09T08:07:30+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-05-14T09:55:39+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-05-06T17:00:02+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-05-06T13:59:59+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Infectious Diseases","date":"2025-05-06T13:58:50+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}},{"code":"","date":"2025-04-25 15:23:19","doi":"","editorialEvents":[{"type":"decision","content":"Revision requested","date":"2025-05-06T12:17:46+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-05-03T04:27:21+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-05-03T04:25:26+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Infectious Diseases","date":"2025-04-25T15:18:13+00:00","index":"","fulltext":""}],"status":"private","journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a32842e5-0e67-4938-b247-c51a516769da","owner":[],"postedDate":"September 10th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-12-08T16:05:51+00:00","versionOfRecord":{"articleIdentity":"rs-7519458","link":"https://doi.org/10.1186/s12879-025-12258-7","journal":{"identity":"bmc-infectious-diseases","isVorOnly":false,"title":"BMC Infectious Diseases"},"publishedOn":"2025-12-05 15:57:42","publishedOnDateReadable":"December 5th, 2025"},"versionCreatedAt":"2025-09-10 13:44:25","video":"","vorDoi":"10.1186/s12879-025-12258-7","vorDoiUrl":"https://doi.org/10.1186/s12879-025-12258-7","workflowStages":[]},"version":"v2","identity":"rs-7519458","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7519458","identity":"rs-7519458","version":["v2"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}