title: [Plasmablast in the pathology of multiple sclerosis].
abstract: Multiple sclerosis (MS) is an autoimmune disease targeting oligodendrocyte in the central nervous system and involves heterogeneous pathology that yields considerable nonresponders to the first line therapy interferon (IFN)-β. However, determinants for this clinical efficacy have not been elucidated. Interestingly, an MS-like autoimmune disease neuromyelitis optica (NMO) is exclusively resistant to this therapy and mediated by IL-6-dependnet PBs via producing a disease-specific autoantibody against aquaporin 4 (AQP4) on astrocyte. Therefore, we assumed that IFN-β-nonresponsive patients with MS may have the similar B-cell abnormality and found an expansion of circulating PBs in these nonresponders. In addition, these PBs exhibited an IL-6-dependent survival in vitro like those in NMO. Clinical features of such "PB-high" patients were consistent with antoantibody-mediated pathology. Thus, we are administering anti-IL-6 receptor blocking antibody tocilizumab to these intractable patients with MS to achieve precision medicine for MS.
authors.affiliation: Department of Immunology, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP).
authors.forename: Masakazu
authors.initials: M
authors.lastname: Nakamura
authors.forename: Manabu
authors.initials: M
authors.lastname: Araki
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamamura
mesh_terms: D025901:Carboxypeptidase B2; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology; D009103:Multiple Sclerosis / Q000276:immunology / Q000473:pathology*; D010950:Plasma Cells / Q000473:pathology*
chemical_list: D016899:Interferon-beta; C585364:CPB2 protein, human; D025901:Carboxypeptidase B2