title: Immunophenotyping of cerebrospinal fluid cells in multiple sclerosis: in search of biomarkers.
abstract: OBJECTIVE
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  All of the articles have shown CSF pleocytosis in MS. Interesting results include CSF enrichment of helper T cells (subtypes TH1 and TH17) and regulatory T cells, as well 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
  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.
authors.affiliation: Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School, Hannover, Germany.
authors.forename: Sascha
authors.initials: S
authors.lastname: Alvermann
authors.affiliation: Department of Pediatric Pneumology and Neonatology, Hannover Medical School, Hannover, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Hennig
authors.affiliation: Neurology Section, VA North Texas Health Care System, Medical Service Dallas, VA Medical Center, Dallas4Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas.
authors.forename: Olaf
authors.initials: O
authors.lastname: Stüve
authors.affiliation: Department of Neurology, University of Münster, Münster, Germany.
authors.forename: Heinz
authors.initials: H
authors.lastname: Wiendl
authors.affiliation: Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School, Hannover, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Stangel
mesh_terms: D015415:Biomarkers / Q000134:cerebrospinal fluid*; D006801:Humans; D016130:Immunophenotyping / Q000379:methods*; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid* / Q000276:immunology* / Q000473:pathology
chemical_list: D015415:Biomarkers