Flow cytometry identifies changes in peripheral and intrathecal lymphocyte patterns in CNS autoimmune disorders and primary CNS malignancies

  1. Räuber, Saskia
  2. Schulte-Mecklenbeck, Andreas
  3. Willison, Alice
  4. Hagler, Ramona
  5. Jonas, Marius
  6. Pul, Duygu
  7. Masanneck, Lars
  8. Schroeter, Christina B.
  9. Golombeck, Kristin S.
  10. Lichtenberg, Stefanie
  11. Strippel, Christine
  12. Gallus, Marco
  13. Dik, Andre
  14. Kerkhoff, Ruth
  15. Barman, Sumanta
  16. Weber, Katharina J.
  17. Kovac, Stjepana
  18. Korsen, Melanie
  19. Pawlitzki, Marc
  20. Goebels, Norbert
  21. Ruck, Tobias
  22. Gross, Catharina C.
  23. Paulus, Werner
  24. Reifenberger, Guido
  25. Hanke, Michael
  26. Grauer, Oliver
  27. Rapp, Marion
  28. Sabel, Michael
  29. Wiendl, Heinz
  30. Meuth, Sven G.
  31. Melzer, Nico

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1000 Titel
  • Flow cytometry identifies changes in peripheral and intrathecal lymphocyte patterns in CNS autoimmune disorders and primary CNS malignancies
1000 Autor/in
  1. Räuber, Saskia |
  2. Schulte-Mecklenbeck, Andreas |
  3. Willison, Alice |
  4. Hagler, Ramona |
  5. Jonas, Marius |
  6. Pul, Duygu |
  7. Masanneck, Lars |
  8. Schroeter, Christina B. |
  9. Golombeck, Kristin S. |
  10. Lichtenberg, Stefanie |
  11. Strippel, Christine |
  12. Gallus, Marco |
  13. Dik, Andre |
  14. Kerkhoff, Ruth |
  15. Barman, Sumanta |
  16. Weber, Katharina J. |
  17. Kovac, Stjepana |
  18. Korsen, Melanie |
  19. Pawlitzki, Marc |
  20. Goebels, Norbert |
  21. Ruck, Tobias |
  22. Gross, Catharina C. |
  23. Paulus, Werner |
  24. Reifenberger, Guido |
  25. Hanke, Michael |
  26. Grauer, Oliver |
  27. Rapp, Marion |
  28. Sabel, Michael |
  29. Wiendl, Heinz |
  30. Meuth, Sven G. |
  31. Melzer, Nico |
1000 Verlag BioMed Central
1000 Erscheinungsjahr 2024
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2024-11-04
1000 Erschienen in
1000 Quellenangabe
  • 21(1):286
1000 Copyrightjahr
  • 2024
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1186/s12974-024-03269-3 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536547/ |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • <jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>Immune dysregulation is a hallmark of autoimmune diseases of the central nervous system (CNS), characterized by an excessive immune response, and primary CNS tumors (pCNS-tumors) showing a highly immunosuppressive parenchymal microenvironment.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>Aiming to provide novel insights into the pathogenesis of CNS autoimmunity and cerebral tumor immunity, we analyzed the peripheral blood (PB) and cerebrospinal fluid (CSF) of 81 autoimmune limbic encephalitis (ALE), 148 relapsing–remitting multiple sclerosis (RRMS), 33 IDH-wildtype glioma, 9 primary diffuse large B cell lymphoma of the CNS (CNS-DLBCL), and 110 controls by flow cytometry (FC). Additionally, an in-depth immunophenotyping of the PB from an independent cohort of 20 RRMS and 18 IDH-wildtype glioblastoma patients compared to 19 controls was performed by FC combined with unsupervised computational approaches.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>We identified alterations in peripheral and intrathecal adaptive immunity, mainly affecting the T cell (Tc) but also the B cell (Bc) compartment in ALE, RRMS, and pCNS-tumors compared to controls. ALE, RRMS, and pCNS-tumors featured higher expression of the T cell activation marker HLA-DR, which was even more pronounced in pCNS-tumors than in ALE or RRMS. Glioblastoma patients showed signs of T cell exhaustion that were not visible in RRMS patients. In-depth characterization of the PB revealed differences mainly in the T effector and memory compartment between RRMS and glioblastoma patients and similar alterations in the Bc compartment, including atypical Bc, CD19<jats:sup>+</jats:sup>CD20<jats:sup>−</jats:sup> double negative Bc, and plasma cells. PB and CSF mFC together with CSF routine parameters could reliably differentiate ALE and RRMS from pCNS-tumors facilitating early diagnosis and treatment.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>ALE, RRMS, and pCNS-tumors show distinct but partially overlapping changes mainly in HLA-DR<jats:sup>+</jats:sup> Tc, memory Tc, exhausted Tc, and Bc subsets providing insights into disease pathogenesis. Moreover, mFC shows diagnostic potential facilitating early diagnosis and treatment.</jats:p> </jats:sec><jats:sec> <jats:title>Graphical Abstract</jats:title> </jats:sec>
1000 Sacherschließung
lokal Lymphocytes/metabolism [MeSH]
lokal Female [MeSH]
lokal Autoimmune Diseases of the Nervous System/diagnosis [MeSH]
lokal Aged [MeSH]
lokal Adult [MeSH]
lokal Humans [MeSH]
lokal Autoimmune limbic encephalitis
lokal Middle Aged [MeSH]
lokal Glioblastoma
lokal Flow Cytometry/methods [MeSH]
lokal Central Nervous System Neoplasms/cerebrospinal fluid [MeSH]
lokal Autoimmune Diseases of the Nervous System/cerebrospinal fluid [MeSH]
lokal Male [MeSH]
lokal Multidimensional flow cytometry
lokal Lymphocytes/immunology [MeSH]
lokal Research
lokal Young Adult [MeSH]
lokal Central Nervous System Neoplasms/immunology [MeSH]
lokal Relapsing–remitting multiple sclerosis
lokal Central Nervous System Neoplasms/diagnosis [MeSH]
lokal Primary diffuse large B cell lymphoma of the CNS
lokal Autoimmune Diseases of the Nervous System/immunology [MeSH]
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
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1000 Förderer
  1. Research Committee of the Faculty of Medicine of the Heinrich Heine University Düsseldorf |
  2. Mildred Scheel Career Center Frankfurt |
  3. Innovative Medizinische Forschung |
  4. German Federal Ministry of Education and Research |
  5. Universitätsklinikum Düsseldorf. Anstalt öffentlichen Rechts |
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  2. 1000 joinedFunding-child
    1000 Förderer Mildred Scheel Career Center Frankfurt |
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  3. 1000 joinedFunding-child
    1000 Förderer Innovative Medizinische Forschung |
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  4. 1000 joinedFunding-child
    1000 Förderer German Federal Ministry of Education and Research |
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    1000 Förderer Universitätsklinikum Düsseldorf. Anstalt öffentlichen Rechts |
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1000 Erstellt am 2025-07-04T02:06:36.115+0200
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