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.