Suppressed pro-inflammatory properties of circulating B cells in patients with multiple sclerosis treated with fingolimod, based on altered proportions of B-cell subpopulations

Clin Immunol. 2014 Apr;151(2):127-35. doi: 10.1016/j.clim.2014.02.001. Epub 2014 Feb 14.

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.

Keywords: B cells; CD80; Cytokine; Fingolimod; Multiple sclerosis; Transitional B cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • B-Lymphocyte Subsets / drug effects*
  • B-Lymphocyte Subsets / immunology
  • B-Lymphocyte Subsets / physiology
  • B7-1 Antigen / blood
  • Case-Control Studies
  • Chemotaxis, Leukocyte / drug effects
  • Chemotaxis, Leukocyte / physiology
  • Female
  • Fingolimod Hydrochloride
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Inflammation / immunology
  • Inflammation / metabolism
  • Interleukin-10 / blood
  • Male
  • Middle Aged
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / metabolism
  • Propylene Glycols / therapeutic use*
  • Receptors, CCR7 / blood
  • Sphingosine / analogs & derivatives*
  • Sphingosine / therapeutic use
  • Tumor Necrosis Factor-alpha / blood

Substances

  • B7-1 Antigen
  • CCR7 protein, human
  • Immunosuppressive Agents
  • Propylene Glycols
  • Receptors, CCR7
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Fingolimod Hydrochloride
  • Sphingosine