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Sera from remitting and secondary progressive multiple sclerosis patients disrupt the blood-brain barrier

Fumitaka Shimizu1, Ayako Tasaki1, Yasuteru Sano1

  • 1Department of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine, Ube, Japan.

Plos One
|April 2, 2014
PubMed
Abstract

Insights

Multiple sclerosis (MS) progression involves blood-brain barrier (BBB) damage. Patient sera from relapse-remitting MS (RRMS) and secondary progressive MS (SPMS) impair BBB integrity by affecting tight junctions and increasing VCAM-1, suggesting novel therapeutic targets.

Area of Science:

  • Neuroimmunology
  • Vascular Biology
  • Demyelinating Diseases

Background:

  • Pathological destruction of the blood-brain barrier (BBB) is a key event in multiple sclerosis (MS) pathogenesis.
  • Understanding BBB malfunction mechanisms in MS is crucial for developing effective treatments.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying BBB dysfunction in patients with relapse-remitting MS (RRMS) and secondary progressive MS (SPMS).
  • To analyze the impact of patient sera on BBB components, including tight junction proteins and VCAM-1.

Main Methods:

  • Human brain microvascular endothelial cells (BMECs) were treated with sera from RRMS (relapse and stable phases) and SPMS patients.
  • Evaluated changes in claudin-5 expression, transendothelial electrical resistance (TEER), vascular cell adhesion protein-1 (VCAM-1) expression, and matrix metalloproteinase (MMP) secretion.

Main Results:

  • Sera from RRMS-relapse and SPMS patients reduced claudin-5 expression and TEER in BMECs.
  • MMP-2/9 secretion increased in RRMS-relapse, and immunoglobulin G (IgG) from SPMS sera also decreased claudin-5 and TEER.
  • All MS patient sera and IgG increased VCAM-1 expression in BMECs.

Conclusions:

  • Autocrine MMP-2/9 upregulation or autoantibodies against BMECs in MS sera compromise BBB integrity.
  • Increased VCAM-1 expression in RRMS-stable and SPMS indicates VCAM-1 as a potential therapeutic target for MS, including later stages.

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