title: Changes in B- and T-lymphocyte and chemokine levels with rituximab treatment in multiple sclerosis.
abstract: BACKGROUND
  B cells are implicated in the pathogenesis of multiple sclerosis. A beneficial effect of B-cell depletion using rituximab has been shown, but the complete mechanism of action for this drug is unclear.
  
  
  OBJECTIVE
  To determine the relationship between T and B cells and changes in cerebrospinal fluid (CSF) chemokine levels with rituximab, a monoclonal antibody that targets CD20.
  
  
  METHODS
  Phase 2 trial of rituximab as an add-on therapy.
  
  
  METHODS
  The John L. Trotter Multiple Sclerosis Center, Washington University. Participants and Intervention Thirty subjects who had relapsing-remitting multiple sclerosis with clinical and magnetic resonance imaging activity despite treatment with an immunomodulatory drug received 4 weekly doses of rituximab (375 mg/m(2)).
  
  
  METHODS
  Lumbar puncture was performed before and after rituximab infusions in 26 subjects. Levels of B and T lymphocytes in the CSF were enumerated by flow cytometry, and chemoattractant levels were measured by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  After rituximab administration, CSF B-cell levels were decreased or undetectable in all subjects, and CSF T-cell levels were reduced in 21 subjects (81%). The mean reduction in CSF cellularity was 95% for B cells and 50% for T cells. After rituximab infusion, CSF CXCL13 and CCL19 levels decreased (P = .002 and P = .03, respectively). The proportional decline in CSF T-cell levels correlated with the proportional decrease in CXCL13 levels (r = 0.45; P = .03), suggesting a possible relationship. The CSF IgG index, IgG concentration, and oligoclonal band number were unchanged following treatment.
  
  
  CONCLUSIONS
  In subjects with multiple sclerosis, B cells are critical for T-cell trafficking into the central nervous system and may alter the process by influencing chemokine production within the central nervous system.
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Piccio
authors.forename: Robert T
authors.initials: RT
authors.lastname: Naismith
authors.forename: Kathryn
authors.initials: K
authors.lastname: Trinkaus
authors.forename: Robyn S
authors.initials: RS
authors.lastname: Klein
authors.forename: Becky J
authors.initials: BJ
authors.lastname: Parks
authors.forename: Jeri A
authors.initials: JA
authors.lastname: Lyons
authors.forename: Anne H
authors.initials: AH
authors.lastname: Cross
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000473:pathology; D000069283:Rituximab; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000187:drug effects*; D013997:Time Factors; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D016207:Cytokines; D007155:Immunologic Factors; D000069283:Rituximab