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

Titel:Flow cytometry identifies changes in peripheral and intrathecal lymphocyte patterns in CNS autoimmune disorders and primary CNS malignancies
URL für Lesezeichen:https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=67932
URN (NBN):urn:nbn:de:hbz:061-20241209-121853-7
Kollektion:Publikationen
Sprache:Englisch
Dokumententyp:Wissenschaftliche Texte » Artikel, Aufsatz
Medientyp:Text
Autoren: Räuber, Saskia [Autor]
Schulte-Mecklenbeck, Andreas [Autor]
Willison, Alice Grizzel [Autor]
Hagler, Ramona [Autor]
Jonas, Marius [Autor]
Pul, Duygu [Autor]
Masanneck, Lars [Autor]
Schroeter, Christina B. [Autor]
Golombeck, Kristin S. [Autor]
Lichtenberg, Stefanie [Autor]
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Dateien vom 09.12.2024 / geändert 09.12.2024
Stichwörter:Glioblastoma, Relapsing–remitting multiple sclerosis, Multidimensional flow cytometry, Autoimmune limbic encephalitis, Primary diffuse large B cell lymphoma of the CNS
Beschreibung:Background

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.
Methods

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.
Results

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+CD20− 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.
Conclusions

ALE, RRMS, and pCNS-tumors show distinct but partially overlapping changes mainly in HLA-DR+ Tc, memory Tc, exhausted Tc, and Bc subsets providing insights into disease pathogenesis. Moreover, mFC shows diagnostic potential facilitating early diagnosis and treatment.
Rechtliche Vermerke:Originalveröffentlichung:
Räuber, S., Schulte-Mecklenbeck, A., Willison, A. G., Hagler, R., Jonas, M., Pul, D., Masanneck, L., Menskes, C. B., Golombeck, K. S., Bock, S., Strippel, C., Gallus, M., Dik, A., Kerkhoff, R., Barman, S., Weber, K. J., Kovac, S., Korsen, M., Pawlitzki, M., … Melzer, N. (2024). Flow cytometry identifies changes in peripheral and intrathecal lymphocyte patterns in CNS autoimmune disorders and primary CNS malignancies. Journal of Neuroinflammation, 21, Article 286. https://doi.org/10.1186/s12974-024-03269-3
Lizenz:Creative Commons Lizenzvertrag
Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung 4.0 International Lizenz
Fachbereich / Einrichtung:Medizinische Fakultät
Dokument erstellt am:09.12.2024
Dateien geändert am:09.12.2024
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