Specific myeloid signatures in peripheral blood differentiate active and rare clinical phenotypes of multiple sclerosis.

Autor:	Vakrakou AG; Demyelinating Diseases Unit, 1st Department of Neurology, School of Medicine, Aeginition Hospital, National and Kapodistrian University of Athens, Athens, Greece.; Department of Neuropathology, University of Göttingen Medical Center, Göttingen, Germany., Paschalidis N; Mass Cytometry-CyTOF Laboratory, Center for Clinical Research, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece., Pavlos E; Center for Clinical Research, Experimental Surgery and Translational Research Biomedical Research Foundation of the Academy of Athens, Athens, Greece.; Division of Basic Sciences, University of Crete Medical School, Heraklion, Greece., Giannouli C; Center for Clinical Research, Experimental Surgery and Translational Research Biomedical Research Foundation of the Academy of Athens, Athens, Greece., Karathanasis D; Demyelinating Diseases Unit, 1st Department of Neurology, School of Medicine, Aeginition Hospital, National and Kapodistrian University of Athens, Athens, Greece., Tsipota X; Demyelinating Diseases Unit, 1st Department of Neurology, School of Medicine, Aeginition Hospital, National and Kapodistrian University of Athens, Athens, Greece., Velonakis G; Research Unit of Radiology, 2nd Department of Radiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece., Stadelmann-Nessler C; Department of Neuropathology, University of Göttingen Medical Center, Göttingen, Germany., Evangelopoulos ME; Demyelinating Diseases Unit, 1st Department of Neurology, School of Medicine, Aeginition Hospital, National and Kapodistrian University of Athens, Athens, Greece., Stefanis L; Demyelinating Diseases Unit, 1st Department of Neurology, School of Medicine, Aeginition Hospital, National and Kapodistrian University of Athens, Athens, Greece., Kilidireas C; Demyelinating Diseases Unit, 1st Department of Neurology, School of Medicine, Aeginition Hospital, National and Kapodistrian University of Athens, Athens, Greece.; Department of Neurology, Henry Dunant Hospital Center, Athens, Greece.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2023 Jan 25; Vol. 14, pp. 1071623. Date of Electronic Publication: 2023 Jan 25 (Print Publication: 2023).
DOI:	10.3389/fimmu.2023.1071623
Abstrakt:	Current understanding of Multiple Sclerosis (MS) pathophysiology implicates perturbations in adaptive cellular immune responses, predominantly T cells, in Relapsing-Remitting forms (RRMS). Nevertheless, from a clinical perspective MS is a heterogeneous disease reflecting the heterogeneity of involved biological systems. This complexity requires advanced analysis tools at the single-cell level to discover biomarkers for better patient-group stratification. We designed a novel 44-parameter mass cytometry panel to interrogate predominantly the role of effector and regulatory subpopulations of peripheral blood myeloid subsets along with B and T-cells (excluding granulocytes) in MS, assessing three different patient cohorts: RRMS, PPMS (Primary Progressive) and Tumefactive MS patients (TMS) (n=10, 8, 14 respectively). We further subgrouped our cohort into inactive or active disease stages to capture the early underlying events in disease pathophysiology. Peripheral blood analysis showed that TMS cases belonged to the spectrum of RRMS, whereas PPMS cases displayed different features. In particular, TMS patients during a relapse stage were characterized by a specific subset of CD11c+CD14+ CD33+, CD192+, CD172+-myeloid cells with an alternative phenotype of monocyte-derived macrophages (high arginase-1, CD38, HLA-DR-low and endogenous TNF-a production). Moreover, TMS patients in relapse displayed a selective CD4 T-cell lymphopenia of cells with a Th2-like polarised phenotype. PPMS patients did not display substantial differences from healthy controls, apart from a trend toward higher expansion of NK cell subsets. Importantly, we found that myeloid cell populations are reshaped under effective disease-modifying therapy predominantly with glatiramer acetate and to a lesser extent with anti-CD20, suggesting that the identified cell signature represents a specific therapeutic target in TMS. The expanded myeloid signature in TMS patients was also confirmed by flow cytometry. Serum neurofilament light-chain levels confirmed the correlation of this myeloid cell signature with indices of axonal injury. More in-depth analysis of myeloid subsets revealed an increase of a subset of highly cytolytic and terminally differentiated NK cells in PPMS patients with leptomeningeal enhancement (active-PPMS), compared to those without (inactive-PPMS). We have identified previously uncharacterized subsets of circulating myeloid cells and shown them to correlate with distinct disease forms of MS as well as with specific disease states (relapse/remission). Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Vakrakou, Paschalidis, Pavlos, Giannouli, Karathanasis, Tsipota, Velonakis, Stadelmann-Nessler, Evangelopoulos, Stefanis and Kilidireas.)
Databáze:	MEDLINE
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