Mass Cytometry of CSF Identifies an MS-Associated B-cell Population

Area of Science:

• Immunology
• Neuroscience
• Biochemistry

Background:

• Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system.
• The precise immune cell populations and molecular mechanisms underlying MS pathogenesis remain incompletely understood.
• Deep immune phenotyping and analysis of soluble factors in cerebrospinal fluid (CSF) are crucial for identifying MS-specific biomarkers.

Purpose of the Study:

• To identify an MS-specific immune cell population using deep immune phenotyping.
• To correlate identified immune cells with soluble signaling molecules in the CSF of MS patients.
• To advance the understanding of immune system involvement in MS.

Main Methods:

• Paired blood and CSF samples from 39 MS patients were analyzed using mass cytometry (cytometry by time of flight) for surface marker expression.
• Concentrations of 296 signaling molecules in CSF were measured using proximity extension assay.
• Unsupervised algorithmic informatics was employed for data analysis.

Main Results:

• A distinct B-cell population expressing CD49d, CD69, CD27, CXCR3, and human leukocyte antigen (HLA)-DR was identified and strongly associated with MS.
• Elevated levels of B-cell-related factors, particularly FCRL2, were observed in MS CSF, especially in early disease stages.
• Decreased levels of B-cell activating factor (BAFF) and reduced proteins involved in neural plasticity were noted in MS.

Conclusions:

• Both cellular and soluble components of CSF in MS are characterized by B-cell-related markers.
• The identified B-cell phenotype represents the strongest candidate for an MS-specific cell type.
• These findings highlight the significant role of B cells in MS pathophysiology.