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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2024

Open Access 01-12-2024 | Multiple Sclerosis | Research

Soluble CD27 is an intrathecal biomarker of T-cell-mediated lesion activity in multiple sclerosis

Authors: Maria T. Cencioni, Roberta Magliozzi, Ilaria Palmisano, Keittisak Suwan, Antonella Mensi, Laura Fuentes-Font, Luisa M. Villar, José I. Fernández-Velasco, Noelia Villarrubia Migallón, Lucienne Costa-Frossard, Enric Monreal, Rehiana Ali, Marina Romozzi, Nicholas Mazarakis, Richard Reynolds, Richard Nicholas, Paolo A. Muraro

Published in: Journal of Neuroinflammation | Issue 1/2024

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Abstract

Objective

Soluble CD27 is a promising cerebrospinal fluid inflammatory biomarker in multiple sclerosis. In this study, we investigate relevant immune and neuro-pathological features of soluble CD27 in multiple sclerosis.

Methods

Protein levels of soluble CD27 were correlated to inflammatory cell subpopulations and inflammatory cytokines and chemokines detected in cerebrospinal fluid of 137 patients with multiple sclerosis and 47 patients with inflammatory and non-inflammatory neurological disease from three independent cohorts. Production of soluble CD27 was investigated in cell cultures of activated T and B cells and CD27-knockout T cells. In a study including matched cerebrospinal fluid and post-mortem brain tissues of patients with multiple sclerosis and control cases, levels of soluble CD27 were correlated with perivascular and meningeal infiltrates and with neuropathological features.

Results

We demonstrate that soluble CD27 favours the differentiation of interferon-γ-producing T cells and is released through a secretory mechanism activated by TCR engagement and regulated by neutral sphingomyelinase. We also show that the levels of soluble CD27 correlate with the representation of inflammatory T cell subsets in the CSF of patients with relapsing-remitting multiple sclerosis and with the magnitude of perivascular and meningeal CD27 + CD4 + and CD8 + T cell infiltrates in post-mortem central nervous system tissue, defining a subgroup of patients with extensive active inflammatory lesions.

Interpretation

Our results demonstrate that soluble CD27 is a biomarker of disease activity, potentially informative for personalized treatment and monitoring of treatment outcomes.
Appendix
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Metadata
Title
Soluble CD27 is an intrathecal biomarker of T-cell-mediated lesion activity in multiple sclerosis
Authors
Maria T. Cencioni
Roberta Magliozzi
Ilaria Palmisano
Keittisak Suwan
Antonella Mensi
Laura Fuentes-Font
Luisa M. Villar
José I. Fernández-Velasco
Noelia Villarrubia Migallón
Lucienne Costa-Frossard
Enric Monreal
Rehiana Ali
Marina Romozzi
Nicholas Mazarakis
Richard Reynolds
Richard Nicholas
Paolo A. Muraro
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2024
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-024-03077-9

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