Comprehensive cerebrospinal fluid analysis indicates key roles for B cells in multiple sclerosis
Fernandez Zapata, C.; Otto, C.; Gallaccio, G.; Chen, Q.; Wang, M.; Uluvar, B.; Teves, M.; Samol, C.; Buthut, M.; Boesl, F.; Dehlinger, A.; Jang, G.; Boettcher, C.; Radbruch, H.; Priller, J.; Schindler, P.; Raposo, C.; Shippling, S.; Pedotti, R.; Kunkel, D.; Pietzner, M.; Franke, C.; Oefner, P.; Gronwald, W.; Pruess, H.; Lohmeier, J.; Paul, F.; Ruprecht, K.; Boettcher, C.
Show abstract
Multiple sclerosis (MS) is a complex inflammatory and neurodegenerative disease of the central nervous system (CNS) with a multifaceted pathophysiology, likely involving a variety of mechanisms and effectors. To characterize the spectrum of cellular and molecular factors involved in MS at an unprecedented level, we here performed a comprehensive analysis of cerebrospinal fluid (CSF) and peripheral blood using multiple high-dimensional technologies, including mass cytometry, metabolomics and proteomics (NULISA and Olink Explore(R) 3072). Enriched B cells and proteins involved in B cell functions in the CSF separated MS patients from other neurological disease entities. Specific B cell subpopulations and molecular markers including gut-microbiota-derived metabolites and neurofilament light protein, a marker of neuroaxonal damage, in CSF correlated with clinical (acute vs. stable disease) and/or radiological (gadolinium enhancement) disease activity. Altogether, unbiased broad phenotyping suggests key roles of diverse B subpopulations and B cell related molecular markers in MS, which are associated with both, inflammatory and degenerative aspects of the disease and may serve as disease activity and treatment response biomarkers.
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