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

Authors :
Räuber, Saskia
Schulte-Mecklenbeck, Andreas
Willison, Alice
Hagler, Ramona
Jonas, Marius
Pul, Duygu
Masanneck, Lars
Schroeter, Christina B.
Golombeck, Kristin S.
Lichtenberg, Stefanie
Strippel, Christine
Gallus, Marco
Dik, Andre
Kerkhoff, Ruth
Barman, Sumanta
Weber, Katharina J.
Kovac, Stjepana
Korsen, Melanie
Pawlitzki, Marc
Goebels, Norbert
Source :
Journal of Neuroinflammation; 11/4/2024, Vol. 21 Issue 1, p1-21, 21p
Publication Year :
2024

Abstract

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<superscript>+</superscript>CD20<superscript>−</superscript> 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<superscript>+</superscript> Tc, memory Tc, exhausted Tc, and Bc subsets providing insights into disease pathogenesis. Moreover, mFC shows diagnostic potential facilitating early diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
17422094
Volume :
21
Issue :
1
Database :
Complementary Index
Journal :
Journal of Neuroinflammation
Publication Type :
Academic Journal
Accession number :
180653629
Full Text :
https://doi.org/10.1186/s12974-024-03269-3