Academic Journal
Multiparameter flow cytometry of CSF identifies elevated CD8+ effector memory and TEMRA T-cells in immune-mediated neurologic disorders.
| Τίτλος: | Multiparameter flow cytometry of CSF identifies elevated CD8+ effector memory and TEMRA T-cells in immune-mediated neurologic disorders. |
|---|---|
| Συγγραφείς: | Wu D; Division of Neuroimmunology, Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, United States., Zhang S; Department of Biomedical Engineering, Stanford University, Stanford, CA, United States., Jamal YA; Department of Pathology, Stanford University, Stanford, CA, United States., Sarkar TT; Division of Neuroimmunology, Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, United States., Tomczak A; Division of Neuroimmunology, Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, United States., Sumera J; Division of Neuroimmunology, Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, United States., Oak J; Department of Pathology, Stanford University, Stanford, CA, United States., Melamed E; Division of Neuroimmunology, Department of Neurology, University Texas of Austin, Austin, TX, United States., Nie E; Division of Neuroimmunology, Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, United States., Galetta K; Division of Neuroimmunology, Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, United States., McDonald J; Division of Neuroimmunology, Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, United States., Lock C; Division of Neuroimmunology, Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, United States., Kipp L; Division of Neuroimmunology, Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, United States., Dunn J; Division of Neuroimmunology, Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, United States., Han M; Division of Neuroimmunology, Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, United States. |
| Πηγή: | Journal of neuropathology and experimental neurology [J Neuropathol Exp Neurol] 2026 Oct 01; Vol. 85 (10), pp. 1141-1155. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Oxford University Press Country of Publication: England NLM ID: 2985192R Publication Model: Print Cited Medium: Internet ISSN: 1554-6578 (Electronic) Linking ISSN: 00223069 NLM ISO Abbreviation: J Neuropathol Exp Neurol Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2016- : Oxford, England : Oxford University Press Original Publication: Lawrence, Ks : Association of the journal of neuropathology and experimental neurology |
| Ιατρικοί όροι (MeSH): | CD8-Positive T-Lymphocytes*/immunology , Immunologic Memory*/immunology , Nervous System Diseases*/immunology , Nervous System Diseases*/cerebrospinal fluid , Memory T Cells*/immunology , T-Lymphocyte Subsets*/immunology, Flow Cytometry/methods ; Biomarkers/cerebrospinal fluid ; Humans ; Female ; Male ; Middle Aged ; Adult ; Aged |
| Περίληψη: | Conventional CSF markers often fail to distinguish immune-mediated neurologic disorders (IMNDs) from non-immune-mediated neurologic disorders (N-IMNDs). We performed multiparametric flow cytometric profiling of CSF T-cell developmental subsets in 37 IMND patients and 10 N-IMND controls to identify IMND-associated T-cell signatures. CSF CD8+ T-cells were detectable in 86% (32/37) of IMND patients versus 0% (0/10) of N-IMND controls (Padj < .001). Among CD8+ T-cell-positive IMND cases, effector memory (CD45RA-CCR7-, median, 65.0%; IQR, 45.5%-73.5%) and terminally differentiated effector memory T-cells (TEMRA, CD45RA+CCR7-, median, 35.0%; IQR, 0%-49.5%) predominated. Hierarchical clustering demonstrated significant separation between IMND and N-IMND driven by CD8+ T-cell subset profiles (R2 = 0.165, P = .001), whereas CD4+ T-cell subsets showed no disease-associated clustering. Paired blood-CSF analysis in 6 treatment-naïve IMND patients revealed compartmentalized enrichment of CD8+ effector memory (blood median 19.2%; IQR, 6.4%-26.9%; CSF median 47.3%; IQR, 42.2%-53.7%; P = .031), confirming CNS-restricted CD8+ T-cell activation. These findings identify CSF CD8+ effector memory profiles as a potential biomarker distinguishing IMNDs from N-IMNDs that may complement conventional biomarkers for CNS autoimmunity. (© The Author(s) 2026. Published by Oxford University Press on behalf of American Association of Neuropathologists, Inc. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.) |
| Grant Information: | FAN-2207 to 39823 Clinician Scientist Development; National Multiple Sclerosis Society and American Brain Foundation (NMSS-ABF) (to D.W.) and through Project BIG (to T.T.S., A.T., and J.S.), Fishman Family Foundation (M.H.), and Leonore and Dale Meyer Funds (C.B.L. and M.H.); National Multiple Sclerosis Society and American Brain Foundation; Fishman Family Foundation; Leonore and Dale Meyer Funds |
| Contributed Indexing: | Keywords: CSF biomarkers; T-cell; autoimmunity; blood-brain barrier; flow cytometry |
| Substance Nomenclature: | 0 (Biomarkers) |
| Entry Date(s): | Date Created: 20260602 Date Completed: 20260925 Latest Revision: 20260925 |
| Update Code: | 20260925 |
| DOI: | 10.1093/jnen/nlag050 |
| PMID: | 42228087 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1554-6578 |
|---|---|
| DOI: | 10.1093/jnen/nlag050 |