title: Suppressed pro-inflammatory properties of circulating B cells in patients with multiple sclerosis treated with fingolimod, based on altered proportions of B-cell subpopulations.
abstract: The chief therapeutic mechanism of fingolimod in multiple sclerosis (MS) is considered to be sequestration of pathogenic lymphocytes into secondary lymphoid tissues. B cells have recently been recognized as important immune regulators in MS. In this study, the effects of fingolimod on B cells in MS patients were analyzed. MS patients treated with fingolimod (MS-F) had a significantly lower number of B cells in the circulation. The remaining B cells in the blood of MS-F had a reduced proportion of memory B cells and an increased proportion of naïve B cells, expressed lower levels of the costimulatory molecule CD80, and produced less tumor necrosis factor-α and more interleukin-10. These observations in MS-F were based on an increased proportion of the transitional B-cell subpopulation within the naïve B-cell compartment. The observed findings in B cells of MS-F might be related to the therapeutic effect of this drug in MS.
authors.affiliation: Department of Clinical Research, Hokkaido Medical Center, 1-1 Yamanote 5-jo 7-choume, Nishi-ku, Sapporo 063-0005, Japan; Department of Neurology, Hokkaido Medical Center, 1-1 Yamanote 5-jo 7-choume, Nishi-ku, Sapporo 063-0005, Japan. Electronic address: yuseimiyazaki@hok-mc.hosp.go.jp.
authors.forename: Yusei
authors.initials: Y
authors.lastname: Miyazaki
authors.affiliation: Department of Clinical Research, Hokkaido Medical Center, 1-1 Yamanote 5-jo 7-choume, Nishi-ku, Sapporo 063-0005, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Niino
authors.affiliation: Sapporo Neurology Clinic, 2-17 Kita-21-jo Higashi-21-choume, Higashi-ku, Sapporo 065-0021, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Fukazawa
authors.affiliation: Department of Clinical Research, Hokkaido Medical Center, 1-1 Yamanote 5-jo 7-choume, Nishi-ku, Sapporo 063-0005, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Takahashi
authors.affiliation: Department of Neurology, Hokkaido Medical Center, 1-1 Yamanote 5-jo 7-choume, Nishi-ku, Sapporo 063-0005, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nonaka
authors.affiliation: Department of Neurology, Hokkaido Medical Center, 1-1 Yamanote 5-jo 7-choume, Nishi-ku, Sapporo 063-0005, Japan.
authors.forename: Itaru
authors.initials: I
authors.lastname: Amino
authors.affiliation: Department of Neurology, Hokkaido Medical Center, 1-1 Yamanote 5-jo 7-choume, Nishi-ku, Sapporo 063-0005, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Tashiro
authors.affiliation: Department of Neurology, Hokkaido Medical Center, 1-1 Yamanote 5-jo 7-choume, Nishi-ku, Sapporo 063-0005, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Minami
authors.affiliation: Department of Neurology, Hokkaido Medical Center, 1-1 Yamanote 5-jo 7-choume, Nishi-ku, Sapporo 063-0005, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Fujiki
authors.affiliation: Department of Neurology, Hokkaido Medical Center, 1-1 Yamanote 5-jo 7-choume, Nishi-ku, Sapporo 063-0005, Japan.
authors.forename: Shizuki
authors.initials: S
authors.lastname: Doi
authors.affiliation: Department of Neurology, Hokkaido Medical Center, 1-1 Yamanote 5-jo 7-choume, Nishi-ku, Sapporo 063-0005, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Kikuchi
mesh_terms: D000328:Adult; D016175:B-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D018122:B7-1 Antigen / Q000097:blood; D016022:Case-Control Studies; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000502:physiology; D005260:Female; D000068876:Fingolimod Hydrochloride; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D011409:Propylene Glycols / Q000627:therapeutic use*; D054400:Receptors, CCR7 / Q000097:blood; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D018122:B7-1 Antigen; C515370:CCR7 protein, human; D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D054400:Receptors, CCR7; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine
keywords: B cells; CD80; Cytokine; Fingolimod; Multiple sclerosis; Transitional B cells