Immunophenotyping of cerebrospinal fluid cells in multiple sclerosis: In search of biomarkers

IMPORTANCE: Cerebrospinal fluid (CSF) is the compartment in closest proximity to the central nervous system (CNS) parenchyma and might reflect immune pathology in inflammatory CNS disorders like multiple sclerosis (MS). Multiparameter flow cytometry is used to characterize immunological alterations in the CSF of patients with MS. OBJECTIVES: To present a comprehensive review of the cellular alterations in CSF that distinguish MS from physiological conditions and other CNS disorders; integrate relevant findings into a model of leukocyte trafficking in the CNS; highlight treatment-related changes in leukocyte subsets; and evaluate the potential of CSF immunophenotyping in the search of novel biomarkers in MS. EVIDENCE REVIEW: We searched MEDLINE articles published between 1980 and 2013 that include the flow cytometric characterization of leukocyte subsets in the CSF of patients with MS. FINDINGS: All of the articles have shown CSF pleocytosis in MS. Interesting results include CSF enrichment of helper T cells (subtypes T_H1 and T _H17) and regulatory T cells, aswell as intrathecal B-cell differentiation resulting in the generation of antibody-producing plasmablasts and plasma cells. Other leukocyte populations, including natural killer cells, monocytes, and dendritic cells, show alterations as well. Characterization of CSF cells increases our understanding of MS pathogenesis and may provide useful biomarkers for individual prognosis and treatment decisions. However, validation in controlled settings is lacking in most cases. CONCLUSIONS AND RELEVANCE: With the advent of more sophisticated approaches, immunophenotyping of CSF cells in MS might become increasingly important to correlate cellular subsets with different stages of disease activity and remission. An assessment of CSF cell numbers and composition should be incorporated into clinical trials.