title: Disease amelioration with tocilizumab in a treatment-resistant patient with neuromyelitis optica: implication for cellular immune responses.
abstract: BACKGROUND
  Neuromyelitis optica (NMO) is an autoimmune disease of the central nervous system in which aberrant antibody responses to the astrocytic water channel aquaporin 4 have been described. Experimental evidence is emerging that NMO is partly driven by the proinflammatory cytokine interleukin 6 (IL-6), which propagates the survival of disease-specific B cell subclasses, and deviates CD4+ T helper cell differentiation toward IL-17-producing T helper 17 cells. Tocilizumab is a recombinant humanized monoclonal antibody against the IL-6 receptor approved for treatment of rheumatoid arthritis.
  
  
  OBJECTIVE
  To study clinical and paraclinical effects of tocilizumab in a patient with NMO.
  
  
  METHODS
  Case report.
  
  
  METHODS
  Academic neurology department.
  
  
  METHODS
  A patient with highly active aquaporin 4–seropositive NMO who failed numerous immunosuppressive interventions, including high-dose corticosteroids, mitoxantrone, plasma exchange (PE), rituximab (anti-CD20), and alemtuzumab (anti-CD52), before receiving tocilizumab.
  
  
  METHODS
  Clinical disability, magnetic resonance imaging, cytokines and transcription factors levels in the cerebrospinal fluid, and peripheral blood mononuclear cells.
  
  
  RESULTS
  A patient who continued to accumulate neurological disability and magnetic resonance imaging activity while receiving numerous immunoactive therapies stabilized, and eventually improved clinically and on magnetic resonance metrics after treatment initiation with tocilizumab. Treatment and clinical response correlated with a significant reduction of IL-6 levels in the CSF as well as a diminished expression of signal transducer and activator of transcription 3.
  
  
  CONCLUSIONS
  Tocilizumab might be effective in NMO, here in a patient not responding to leukocyte depletion. Our findings further support data that implicate IL-6 as a critical molecule in the immunopathogenesis of NMO, and a critical role for T cells in the pathogenesis of this disorder.
authors.affiliation: Department of Neurology, Heinrich-Heine-University, Moorenstrasse 5, Düsseldorf, Germany. bernd.kieseier@uni-duesseldorf.de
authors.forename: Bernd C
authors.initials: BC
authors.lastname: Kieseier
authors.forename: Olaf
authors.initials: O
authors.lastname: Stüve
authors.forename: Thomas
authors.initials: T
authors.lastname: Dehmel
authors.forename: Norbert
authors.initials: N
authors.lastname: Goebels
authors.forename: Verena I
authors.initials: VI
authors.lastname: Leussink
authors.forename: Anne K
authors.initials: AK
authors.lastname: Mausberg
authors.forename: Marius
authors.initials: M
authors.lastname: Ringelstein
authors.forename: Bernd
authors.initials: B
authors.lastname: Turowski
authors.forename: Orhan
authors.initials: O
authors.lastname: Aktas
authors.forename: Gerald
authors.initials: G
authors.lastname: Antoch
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hartung
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology*; D009471:Neuromyelitis Optica / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C502936:tocilizumab