Treatment response to dimethyl fumarate is characterized by disproportionate CD8+ T cell reduction in MS

Mult Scler. 2018 Apr;24(5):632-641. doi: 10.1177/1352458517703799. Epub 2017 Apr 24.

Abstract

Background: The effect of dimethyl fumarate (DMF) on circulating lymphocyte subsets and their contribution as predictors of clinical efficacy have not yet been investigated in multiple sclerosis (MS).

Objective: To evaluate lymphocytes and lymphocyte subsets (analyzed 6 months after DMF start) in MS patients with and without disease activity after 1 year of treatment in a retrospective study.

Methods: Peripheral blood lymphocyte subsets were analyzed by flow cytometry. Untreated MS patients ( n = 40) were compared to those 6 months after onset of DMF treatment ( n = 51). Clinical and magnetic resonance imaging (MRI) disease activity of DMF-treated patients were assessed in the first year under treatment.

Results: Stable patients showed significantly lower lymphocytes, CD4+ and CD8+ T cells as well as CD19+ B cells compared to active patients under DMF treatment. Furthermore, an increased CD4/CD8 ratio ( p < 0.025) in stable patients indicated a disproportionate reduction of CD8+ T cells relative to CD4+ T cells. Reduced lymphocytes, CD8+ T cells, and CD19+ B cells 6 months after DMF start allowed prediction of the treatment response in the first year.

Conclusion: DMF treatment response is reflected by lower circulating lymphocytes and specific lymphocyte subsets. Changes in the cellular immune profiles under DMF treatment are clinically relevant and might serve as a surrogate marker of treatment response.

Keywords: CD8+ T cells; Multiple sclerosis; dimethyl fumarate; lymphocyte subsets; treatment response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antigens, CD19
  • B-Lymphocytes / immunology
  • CD4-CD8 Ratio
  • CD8-Positive T-Lymphocytes*
  • Cross-Sectional Studies
  • Dimethyl Fumarate / adverse effects
  • Dimethyl Fumarate / therapeutic use*
  • Disease Progression
  • Female
  • Flow Cytometry
  • Follow-Up Studies
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Longitudinal Studies
  • Lymphocyte Count
  • Lymphopenia / etiology
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Multiple Sclerosis / blood
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / immunology*
  • Multiple Sclerosis / pathology
  • ROC Curve
  • Retrospective Studies
  • Statistics, Nonparametric
  • Treatment Outcome
  • Young Adult

Substances

  • Antigens, CD19
  • CD19 molecule, human
  • Immunosuppressive Agents
  • Dimethyl Fumarate