title: Natalizumab analogon therapy is effective in a B cell-dependent multiple sclerosis model.
abstract: OBJECTIVE
  Natalizumab is a humanized monoclonal antibody specific for CD49d receptors of integrins. It inhibits the entry of inflammatory cells into the central nervous system and is approved for the treatment of relapsing-remitting multiple sclerosis (MS). Several lines of evidence indicate an involvement of B cells and plasma cells in MS pathogenesis. However, treatment with the natalizumab analogon PS/2 immunoglobulin G (IgG) has so far only been investigated in T cell-mediated animal models of MS. Due to the importance of B lineage cells in the pathogenesis of MS, the objective of the present study has thus been to analyse the effects of PS/2 IgG in a mouse model of MS with T and B cell cooperation (OSE mice).
  
  
  METHODS
  OSE mice were treated with the natalizumab analogon PS/2 IgG either at disease onset or after peak of disease. Treatment was also performed with PS/2 F(ab')2 fragments.
  
  
  RESULTS
  PS/2 IgG treatment improved the clinical outcome and decreased spinal cord demyelination and immune cell infiltration if given early in the disease course. Treatment increased blood leukocytes and resulted in a partial internalization of CD49d in T and B cells. The therapeutic effects of PS/2 IgG injections were independent of the Fc fragment as F(ab')2 injections were equally beneficial. In contrast, PS/2 IgG was not effective when given late in the disease course.
  
  
  CONCLUSIONS
  Results indicate that natalizumab may also be beneficial in MS with B cell-driven immunopathogenesis.
authors: Department of Neuropathology, University Medical Center, Georg August University, Göttingen, Germany.
authors: Darius
authors: D
authors: Häusler
authors: Department of Neuropathology, University Medical Center, Georg August University, Göttingen, Germany.
authors: Stefan
authors: S
authors: Nessler
authors: Department of Neuropathology, University Medical Center, Georg August University, Göttingen, Germany.
authors: Niels
authors: N
authors: Kruse
authors: Department of Neuropathology, University Medical Center, Georg August University, Göttingen, Germany.
authors: Wolfgang
authors: W
authors: Brück
authors: Department of Neuropathology, University Medical Center, Georg August University, Göttingen, Germany.
authors: Imke
authors: I
authors: Metz
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001665:Binding Sites; D004195:Disease Models, Animal; D007074:Immunoglobulin G / Q000008:administration & dosage; D039441:Integrin alpha4 / Q000276:immunology; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology*; D000069442:Natalizumab / Q000008:administration & dosage*; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology; D066127:White Matter / Q000187:drug effects / Q000473:pathology
chemical_list: D007074:Immunoglobulin G; D000069442:Natalizumab; D039441:Integrin alpha4
keywords: B cells; CD49d; OSE mice; PS/2 antibody; experimental autoimmune encephalomyelitis; multiple sclerosis; natalizumab