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

Objective To identify an MS-specific immune cell population by deep immune phenotyping and relate it to soluble signaling molecules in CSF. Methods We analyzed surface expression of 22 markers in paired blood/CSF samples from 39 patients using mass cytometry (cytometry by time of flight). We also measured the concentrations of 296 signaling molecules in CSF using proximity extension assay. Results were analyzed using highly automated unsupervised algorithmic informatics. Results Mass cytometry objectively identified a B-cell population characterized by the expression of CD49d, CD69, CD27, CXCR3, and human leukocyte antigen (HLA)-DR as clearly associated with MS. Concentrations of the B cell-related factors, notably FCRL2, were increased in MS CSF, especially in early stages of the disease. The B-cell trophic factor B cell activating factor (BAFF) was decreased in MS. Proteins involved in neural plasticity were also reduced in MS. Conclusion When analyzed without a priori assumptions, both the soluble and the cellular compartments of the CSF in MS were characterized by markers related to B cells, and the strongest candidate for an MS-specific cell type has a B-cell phenotype.

Automated summary

Deep immune phenotyping identified a B-cell population associated with multiple sclerosis, with increased levels of B cell-related factors in early disease stages. Soluble signaling molecules related to B cells, including FCRL2 and BAFF, were altered in multiple sclerosis.