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Fingolimod reduces circulating tight-junction protein levels and in vitro peripheral blood mononuclear cells

Pasquale Annunziata1, Chiara Cioni2, Gianni Masi2

  • 1Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy. annunziata@unisi.it.

Scientific Reports
|October 20, 2018
PubMed

Insights

Fingolimod treatment for multiple sclerosis (MS) reduced relapses and active lesions. It also decreased circulating tight-junction proteins, impacting cell migration and potentially the blood-brain barrier (BBB).

Area of Science:

  • Neuroimmunology
  • Cell Biology
  • Biochemistry

Background:

  • Multiple sclerosis (MS) is an autoimmune disease affecting the central nervous system.
  • Fingolimod is an immunomodulatory drug used for MS treatment.
  • The effects of fingolimod on circulating tight-junction (TJ) proteins and peripheral blood mononuclear cell (PBMC) migration are unknown.

Purpose of the Study:

  • To investigate the impact of fingolimod on serum TJ protein levels (occludin, claudin-5, ZO-1) in MS patients.
  • To assess changes in sphingosine-1 phosphate 1 (S1P1) receptor expression and in vitro PBMC migration.
  • To correlate these changes with clinical and MRI parameters during 12 months of fingolimod treatment.

Main Methods:

  • Longitudinal assessment of serum TJ proteins, S1P1 receptor expression on leukocytes, and in vitro PBMC migration in 20 MS patients.
  • Correlation analysis with clinical data and MRI findings (relapse rate, active lesions, disability scores).

Main Results:

  • Fingolimod treatment significantly reduced MS relapse rates and active MRI lesions after 12 months.
  • Serum TJ protein levels, S1P1 receptor expression, and PBMC migratory activity significantly decreased.
  • Specific TJ protein ratios (CLN-5/OCLN, CLN-5/ZO-1) correlated with MRI lesions and disability scores.

Conclusions:

  • Fingolimod may exert in vivo effects on blood-brain barrier (BBB) function and peripheral cell trafficking in MS.
  • These effects could prevent autoreactive cells from entering the brain.
  • Circulating TJ proteins and their ratios may serve as novel biomarkers for BBB status during MS treatment.

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