title: B-cell populations discriminate between pediatric- and adult-onset multiple sclerosis.
abstract: OBJECTIVE
  To comparatively assess the B-cell composition in blood and CSF of patients with pediatric-onset multiple sclerosis (pedMS) and adult-onset multiple sclerosis (adMS).
  
  
  METHODS
  In this cross-sectional study, we obtained blood and CSF samples from 25 patients with pedMS (8-18 years) and 40 patients with adMS (23-65 years) and blood specimens from 66 controls (1-55 years). By using multicolor flow cytometry, we identified naive, transitional, isotype class-switched memory, nonswitched memory, and double-negative memory B-cell subsets as well as plasmablasts (PB) and terminally differentiated plasma cells (PC). Flow cytometric data were compared to concentrations of B-cell-specific cytokines in serum and CSF as determined by ELISA.
  
  
  RESULTS
  Frequencies of circulating naive B-cells decreased with higher age in controls but not in patients with multiple sclerosis (MS). B-cell patterns in CSF differed between pedMS and adMS with an acute relapse: in pedMS-derived CSF samples, high frequencies of nonswitched memory B cells and PB were present, whereas class-switched memory B cells and PC dominated in the CSF of patients with adMS. In pedMS, PB were also elevated in the periphery. Accumulation of PB in the CSF correlated with high intrathecal CXCL-13 levels and augmented intrathecal synthesis of immunoglobulin G and immunoglobulin M.
  
  
  CONCLUSIONS
  We demonstrate distinct changes in intrathecal B-cell homeostasis in patients with pedMS during active disease, which differ from those in adults by an expansion of plasmablasts in blood and CSF and similarly occur in prototypic autoantibody-driven autoimmune disorders. This emphasizes the particular importance of activated B-lymphocyte subsets for disease progression in the earliest clinical stages of MS.
authors.affiliation: Molecular Neuroimmunology Group (A.S., B.B., M.K.-K., S.J., B.W., J.H.), Department of Neurology, University Hospital of Heidelberg, Germany; Sobell Department of Motor Neuroscience and Movement Disorders (B.B.), UCL Institute of Neurology, London, UK; Department of Pediatric Neurology (K.v.E., A.F., C.B., F.E.), University Children's Hospital, Heidelberg; Department of Pediatrics (A.F.), University Medical Center Hamburg-Eppendorf, Hamburg; Child Neurology Practice (C.B.), ATOS Clinic Heidelberg; and Department of Child and Adolescent Medicine (F.E.), St. Vincenz-Krankenhaus, Paderborn, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Schwarz
authors.affiliation: Molecular Neuroimmunology Group (A.S., B.B., M.K.-K., S.J., B.W., J.H.), Department of Neurology, University Hospital of Heidelberg, Germany; Sobell Department of Motor Neuroscience and Movement Disorders (B.B.), UCL Institute of Neurology, London, UK; Department of Pediatric Neurology (K.v.E., A.F., C.B., F.E.), University Children's Hospital, Heidelberg; Department of Pediatrics (A.F.), University Medical Center Hamburg-Eppendorf, Hamburg; Child Neurology Practice (C.B.), ATOS Clinic Heidelberg; and Department of Child and Adolescent Medicine (F.E.), St. Vincenz-Krankenhaus, Paderborn, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Balint
authors.affiliation: Molecular Neuroimmunology Group (A.S., B.B., M.K.-K., S.J., B.W., J.H.), Department of Neurology, University Hospital of Heidelberg, Germany; Sobell Department of Motor Neuroscience and Movement Disorders (B.B.), UCL Institute of Neurology, London, UK; Department of Pediatric Neurology (K.v.E., A.F., C.B., F.E.), University Children's Hospital, Heidelberg; Department of Pediatrics (A.F.), University Medical Center Hamburg-Eppendorf, Hamburg; Child Neurology Practice (C.B.), ATOS Clinic Heidelberg; and Department of Child and Adolescent Medicine (F.E.), St. Vincenz-Krankenhaus, Paderborn, Germany.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Korporal-Kuhnke
authors.affiliation: Molecular Neuroimmunology Group (A.S., B.B., M.K.-K., S.J., B.W., J.H.), Department of Neurology, University Hospital of Heidelberg, Germany; Sobell Department of Motor Neuroscience and Movement Disorders (B.B.), UCL Institute of Neurology, London, UK; Department of Pediatric Neurology (K.v.E., A.F., C.B., F.E.), University Children's Hospital, Heidelberg; Department of Pediatrics (A.F.), University Medical Center Hamburg-Eppendorf, Hamburg; Child Neurology Practice (C.B.), ATOS Clinic Heidelberg; and Department of Child and Adolescent Medicine (F.E.), St. Vincenz-Krankenhaus, Paderborn, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Jarius
authors.affiliation: Molecular Neuroimmunology Group (A.S., B.B., M.K.-K., S.J., B.W., J.H.), Department of Neurology, University Hospital of Heidelberg, Germany; Sobell Department of Motor Neuroscience and Movement Disorders (B.B.), UCL Institute of Neurology, London, UK; Department of Pediatric Neurology (K.v.E., A.F., C.B., F.E.), University Children's Hospital, Heidelberg; Department of Pediatrics (A.F.), University Medical Center Hamburg-Eppendorf, Hamburg; Child Neurology Practice (C.B.), ATOS Clinic Heidelberg; and Department of Child and Adolescent Medicine (F.E.), St. Vincenz-Krankenhaus, Paderborn, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: von Engelhardt
authors.affiliation: Molecular Neuroimmunology Group (A.S., B.B., M.K.-K., S.J., B.W., J.H.), Department of Neurology, University Hospital of Heidelberg, Germany; Sobell Department of Motor Neuroscience and Movement Disorders (B.B.), UCL Institute of Neurology, London, UK; Department of Pediatric Neurology (K.v.E., A.F., C.B., F.E.), University Children's Hospital, Heidelberg; Department of Pediatrics (A.F.), University Medical Center Hamburg-Eppendorf, Hamburg; Child Neurology Practice (C.B.), ATOS Clinic Heidelberg; and Department of Child and Adolescent Medicine (F.E.), St. Vincenz-Krankenhaus, Paderborn, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Fürwentsches
authors.affiliation: Molecular Neuroimmunology Group (A.S., B.B., M.K.-K., S.J., B.W., J.H.), Department of Neurology, University Hospital of Heidelberg, Germany; Sobell Department of Motor Neuroscience and Movement Disorders (B.B.), UCL Institute of Neurology, London, UK; Department of Pediatric Neurology (K.v.E., A.F., C.B., F.E.), University Children's Hospital, Heidelberg; Department of Pediatrics (A.F.), University Medical Center Hamburg-Eppendorf, Hamburg; Child Neurology Practice (C.B.), ATOS Clinic Heidelberg; and Department of Child and Adolescent Medicine (F.E.), St. Vincenz-Krankenhaus, Paderborn, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Bussmann
authors.affiliation: Molecular Neuroimmunology Group (A.S., B.B., M.K.-K., S.J., B.W., J.H.), Department of Neurology, University Hospital of Heidelberg, Germany; Sobell Department of Motor Neuroscience and Movement Disorders (B.B.), UCL Institute of Neurology, London, UK; Department of Pediatric Neurology (K.v.E., A.F., C.B., F.E.), University Children's Hospital, Heidelberg; Department of Pediatrics (A.F.), University Medical Center Hamburg-Eppendorf, Hamburg; Child Neurology Practice (C.B.), ATOS Clinic Heidelberg; and Department of Child and Adolescent Medicine (F.E.), St. Vincenz-Krankenhaus, Paderborn, Germany.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Ebinger
authors.affiliation: Molecular Neuroimmunology Group (A.S., B.B., M.K.-K., S.J., B.W., J.H.), Department of Neurology, University Hospital of Heidelberg, Germany; Sobell Department of Motor Neuroscience and Movement Disorders (B.B.), UCL Institute of Neurology, London, UK; Department of Pediatric Neurology (K.v.E., A.F., C.B., F.E.), University Children's Hospital, Heidelberg; Department of Pediatrics (A.F.), University Medical Center Hamburg-Eppendorf, Hamburg; Child Neurology Practice (C.B.), ATOS Clinic Heidelberg; and Department of Child and Adolescent Medicine (F.E.), St. Vincenz-Krankenhaus, Paderborn, Germany.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Wildemann
authors.affiliation: Molecular Neuroimmunology Group (A.S., B.B., M.K.-K., S.J., B.W., J.H.), Department of Neurology, University Hospital of Heidelberg, Germany; Sobell Department of Motor Neuroscience and Movement Disorders (B.B.), UCL Institute of Neurology, London, UK; Department of Pediatric Neurology (K.v.E., A.F., C.B., F.E.), University Children's Hospital, Heidelberg; Department of Pediatrics (A.F.), University Medical Center Hamburg-Eppendorf, Hamburg; Child Neurology Practice (C.B.), ATOS Clinic Heidelberg; and Department of Child and Adolescent Medicine (F.E.), St. Vincenz-Krankenhaus, Paderborn, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Haas