Differential effects of fingolimod on B-cell populations in multiple sclerosis

Mult Scler. 2014 Sep;20(10):1371-80. doi: 10.1177/1352458514523496. Epub 2014 Feb 13.


Background: Fingolimod is an oral drug approved for multiple sclerosis (MS) with an ability to trap central memory T cells in secondary lymphoid tissues; however, its variable effectiveness in individual patients indicates the need to evaluate its effects on other lymphoid cells.

Objective: To clarify the effects of fingolimod on B-cell populations in patients with MS.

Methods: We analysed blood samples from 9 fingolimod-treated and 19 control patients with MS by flow cytometry, to determine the frequencies and activation states of naive B cells, memory B cells, and plasmablasts.

Results: The frequencies of each B-cell population in peripheral blood mononuclear cells (PBMC) were greatly reduced 2 weeks after starting fingolimod treatment. Detailed analysis revealed a significant reduction in activated memory B cells (CD38(int-high)), particularly those expressing Ki-67, a marker of cell proliferation. Also, we noted an increased proportion of activated plasmablasts (CD138(+)) among whole plasmablasts, in the patients treated with fingolimod.

Conclusions: The marked reduction of Ki-67(+) memory B cells may be directly linked with the effectiveness of fingolimod in treating MS. In contrast, the relative resistance of CD138(+) plasmablasts to fingolimod may be of relevance for understanding the differential effectiveness of fingolimod in individual patients.

Keywords: B cells; CD138; CD38; fingolimod; memory B cell; multiple sclerosis; plasmablast; proliferation; resistance; sphingosine 1-phosphate receptor 1.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-ribosyl Cyclase 1 / metabolism
  • Adult
  • B-Lymphocyte Subsets / drug effects*
  • B-Lymphocyte Subsets / immunology
  • B-Lymphocyte Subsets / metabolism
  • Biomarkers / metabolism
  • Case-Control Studies
  • Cell Proliferation / drug effects
  • Drug Resistance
  • Female
  • Fingolimod Hydrochloride
  • Flow Cytometry
  • Humans
  • Immunologic Memory
  • Immunosuppressive Agents / therapeutic use*
  • Ki-67 Antigen / metabolism
  • Lymphocyte Activation / drug effects
  • Male
  • Membrane Glycoproteins / metabolism
  • Middle Aged
  • Multiple Sclerosis / blood
  • Multiple Sclerosis / diagnosis
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / genetics
  • Multiple Sclerosis / immunology
  • Phenotype
  • Propylene Glycols / therapeutic use*
  • RNA, Messenger / metabolism
  • Receptors, Lysosphingolipid / genetics
  • Receptors, Lysosphingolipid / metabolism
  • Sphingosine / analogs & derivatives*
  • Sphingosine / therapeutic use
  • Sphingosine-1-Phosphate Receptors
  • Syndecan-1 / metabolism
  • Time Factors
  • Treatment Outcome


  • Biomarkers
  • Immunosuppressive Agents
  • Ki-67 Antigen
  • Membrane Glycoproteins
  • Propylene Glycols
  • RNA, Messenger
  • Receptors, Lysosphingolipid
  • S1PR1 protein, human
  • SDC1 protein, human
  • Sphingosine-1-Phosphate Receptors
  • Syndecan-1
  • CD38 protein, human
  • ADP-ribosyl Cyclase 1
  • Fingolimod Hydrochloride
  • Sphingosine