RT Journal Article
SR Electronic
T1 Mass Cytometry of CSF Identifies an MS-Associated B-cell Population
JF Neurology - Neuroimmunology Neuroinflammation
JO Neurol Neuroimmunol Neuroinflamm
FD Lippincott Williams & Wilkins
SP e943
DO 10.1212/NXI.0000000000000943
VO 8
IS 2
A1 David Johansson
A1 Céline Rauld
A1 Julien Roux
A1 Camille Regairaz
A1 Edoardo Galli
A1 Ilaria Callegari
A1 Layla Raad
A1 Annick Waldt
A1 Rachel Cuttat
A1 Guglielmo Roma
A1 Martin Diebold
A1 Burkhard Becher
A1 Jens Kuhle
A1 Tobias Derfuss
A1 José M. Carballido
A1 Nicholas S.R. Sanderson
YR 2021
UL http://nn.neurology.org/content/8/2/e943.abstract
AB 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.BSA=bovine serum albumin; CyTOF=cytometry by time of flight; FDR=false discovery rate; ICOS=inducible T-cell costimulator; PCA=principal component analysis; PEA=proximal extension assay; PBMC=peripheral blood mononuclear cell; PBS=phosphate-buffered saline