title: Immunological markers of optimal response to natalizumab in multiple sclerosis.
abstract: OBJECTIVE
  To explore cell subsets and molecules that changed specifically in patients with multiple sclerosis (MS) who had an optimal response to natalizumab. Natalizumab is a monoclonal antibody that inhibits the migration of activated immune cells to the central nervous system. It shows high efficacy in modifying the natural history of MS and induces freedom of disease activity in about 40% of treated patients with MS.
  
  
  METHODS
  Prospective study of intrathecal immunoglobulin synthesis and cerebrospinal fluid lymphocyte subsets in patients with MS before and 1 year after beginning treatment with natalizumab. We monitored clinical and magnetic resonance imaging activity during a median time of 2 years.
  
  
  METHODS
  Two tertiary hospitals from the Spanish National Health Service.
  
  
  METHODS
  A total of 23 patients with MS.
  
  
  METHODS
  The differences between patients free of disease activity and patients with active disease during treatment.
  
  
  RESULTS
  Of the 23 patients, 10 (43.5%) remained free of disease activity during follow-up. The remaining 13 patients (56.5%) had relapses or new lesions despite natalizumab therapy. We did not find differences in demographic variables or clinical data between both groups prior to natalizumab therapy. All patients showed a decrease in cerebrospinal fluid CD4(+) cells regardless of their response to treatment. Conversely, only patients free of disease activity showed a decrease in local IgM and, to a lesser extent, in IgG synthesis. They also showed lower percentages of B cells, particularly of CD5(+) and plasmablast subsets that virtually disappeared after treatment with natalizumab.
  
  
  CONCLUSIONS
  These data indicate that inhibition of intrathecal antibody synthesis is associated with a complete therapeutic response to natalizumab in patients with aggressive MS.
authors.affiliation: Department of Immunology, Hospital Ramón y Cajal, Carretera de Colmenar Km 9.100, 28034 Madrid, Spain. lvillar.hrc@salud.madrid.org
authors.forename: Luisa M
authors.initials: LM
authors.lastname: Villar
authors.forename: María I
authors.initials: MI
authors.lastname: García-Sánchez
authors.forename: Lucienne
authors.initials: L
authors.lastname: Costa-Frossard
authors.forename: Mercedes
authors.initials: M
authors.lastname: Espiño
authors.forename: Ernesto
authors.initials: E
authors.lastname: Roldán
authors.forename: Dolores
authors.initials: D
authors.lastname: Páramo
authors.forename: Miguel
authors.initials: M
authors.lastname: Lucas
authors.forename: Guillermo
authors.initials: G
authors.lastname: Izquierdo
authors.forename: José C
authors.initials: JC
authors.lastname: Álvarez-Cermeño
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000502:physiology; D015415:Biomarkers; D018956:CD5 Antigens / Q000032:analysis; D018572:Disease-Free Survival; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007958:Leukocyte Count; D008279:Magnetic Resonance Imaging; D008297:Male; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology*; D000069442:Natalizumab; D011446:Prospective Studies; D055502:Secondary Prevention; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D018956:CD5 Antigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D000069442:Natalizumab