Baseline Differences in Minor Lymphocyte Subpopulations may Predict Response to Fingolimod in Relapsing-Remitting Multiple Sclerosis Patients

CNS Neurosci Ther. 2016 Jul;22(7):584-92. doi: 10.1111/cns.12548. Epub 2016 Apr 15.

Abstract

Aims: Fingolimod, oral treatment for relapsing-remitting multiple sclerosis (RRMS), is an agonist of sphingosine and its metabolite S1P that binds their receptors, blocking the egress of lymphocytes from lymph nodes. The aim of this study was immunomonitoring of minor peripheral lymphocyte subpopulations in RRMS patients under treatment with fingolimod and correlation with treatment response.

Methods: Prospective study. T- and B-cell subpopulations were analyzed using multiparametric flow cytometry in peripheral blood from 14 RRMS patients under treatment with fingolimod at baseline, +1, +3, +6, +9, and +12 months of follow-up. Response to therapy was assessed at month +12.

Results: Most changes in minor lymphocyte subpopulations occurred in the first month of treatment and were maintained until the end of follow-up. The basal percentages of recent thymic emigrants (RTEs) and transitional B cells were lower in responder patients than in nonresponders. After 1 month of follow-up, the percentages of late effector memory CD4(+) T cells in peripheral blood were higher in responder patients.

Conclusion: If confirmed in a bigger cohort of patients, analysis of percentages of minor lymphocyte subpopulations in peripheral blood of patients with RRMS prior and after +1 month of treatment might predict clinical response to fingolimod.

Keywords: Fingolimod; Immunomonitoring; Minor lymphocyte subpopulations; Multiple sclerosis; Response to treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Adolescent
  • Adult
  • Analysis of Variance
  • Cytokines / metabolism
  • Disability Evaluation
  • Female
  • Fingolimod Hydrochloride / pharmacology
  • Fingolimod Hydrochloride / therapeutic use*
  • Flow Cytometry
  • Follow-Up Studies
  • Humans
  • Immunosuppressive Agents / pharmacology
  • Immunosuppressive Agents / therapeutic use*
  • Lymphocyte Subsets / classification
  • Lymphocyte Subsets / drug effects*
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Multiple Sclerosis, Relapsing-Remitting / pathology*
  • Phosphoproteins / metabolism
  • Time Factors
  • Young Adult

Substances

  • Adaptor Proteins, Signal Transducing
  • Cytokines
  • EFS protein, human
  • Immunosuppressive Agents
  • Phosphoproteins
  • Fingolimod Hydrochloride