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Early central vs. peripheral immunological and neurobiological effects of fingolimod—a longitudinal study

Abstract

Fingolimod (FTY) is known to have multiple effects on the immune system and the central nervous system (CNS) in patients with multiple sclerosis (MS). In this study, we evaluated the immunological and neurobiological effects of FTY in MS. Blood and cerebrospinal fluid (CSF) samples were collected from 15 MS patients before first FTY administration and after 4 months of FTY therapy. Immunophenotyping and evaluation of sphingosine-1-phosphate (S1P), neurofilament light chain (NFL), S-100 and neuron-specific enolase (NSE) levels were conducted. After 4 months of FTY therapy, absolute cell count in CSF was decreased from 6.33 to 2.43 MPt/l, accompanied by decreases of CD3+ (2.22 to 0.65 MPt/l) and of CD4+ counts (1.60 to 0.39 MPt/l). In blood, CD3+ (1.05 to 0.09 GPt/l), CD4+ (0.80 to 0.02 GPt/l), CD8+ (0.23 to 0.04 GPt/l) and CD19+ (0.21 to 0.01GPt/l) cell counts were as well reduced. CD14+ cell count remained stable over the same period (0.24 to 0.26GPt/l). NFL and S1P levels in CSF and blood were reduced over time (NFL: CSF 1759 to 1359 pg/l, blood 8.42 to 7.36 pg/l; S1P: CSF 2.12 to 0.71 nmol/l, blood 392.1 to 312.9 nmol/l). Strong correlations between CSF and blood NFL levels were observed. Neuronal damage markers such as S-100 (1.86 to 1.69 μg/l) and NSE (9.53 to 8.67 μg/l) were reduced to a lesser degree than other markers. FTY exerted significant effects on immunological and neurobiological markers in the central and peripheral compartment. Decreases in levels of neuroinflammatory and neurodegenerative markers were already evident after 4 months of treatment. Four-month serum NFL level appears to be a useful marker for FTY efficacy that correlates well with changes in the CNS compartment.

Key messages

  • FTY has important immunological effects in both central and peripheral compartments.

  • Cellular effects of FTY effects are more pronounced in the blood than in the CSF.

  • FTY reduces S1P and NFL levels in CSF and serum.

  • Serum NFL appears to be a useful marker for FTY therapy.

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Correspondence to Malgorzata Zendzian-Piotrowska or Tjalf Ziemssen.

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Conflict of interests

TS, RB and MZP have nothing to declare. KA received personal compensation from Novartis, Biogen Idec, Teva, Sanofi and Roche for the consulting service. TZ received personal compensation from Biogen Idec, Bayer, Novartis, Sanofi, Teva, and Synthon for the consulting services. Ziemssen received additional financial support for the research activities from Bayer, Biogen Idec, Novartis, Teva, and Sanofi Aventis.

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Sehr, T., Akgün, K., Proschmann, U. et al. Early central vs. peripheral immunological and neurobiological effects of fingolimod—a longitudinal study. J Mol Med 97, 1263–1271 (2019). https://doi.org/10.1007/s00109-019-01812-x

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  • DOI: https://doi.org/10.1007/s00109-019-01812-x

Keywords

  • Multiple sclerosis
  • Fingolimod
  • CNS
  • S1P
  • CSF
  • Immune cell
  • Monitoring
  • Neurofilament light chain