INTRODUCTION
Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder
(NMOSD) are demyelinating inflammatory diseases of the central nervous
system (CNS)
[1,2]. Many
previous studies have revealed the important roles of inflammatory
mediators, including cytokines, in the pathogenesis of MS and NMOSD
[3-8]. Substances derived from damaged
autologous tissues, called damage-associated molecular patterns (DAMPs),
are attracting attention in the field of autoimmune diseases because
they function as inflammatory mediators when released from cells
[9,10]. We
previously reported increased levels of high mobility group box 1
(HMGB1), a DAMP, in the serum of MS patients and the cerebrospinal fluid
(CSF) from MS and NMOSD [4]. We also
reported a significant positive correlation between CSF HMGB1 levels and
CSF cells in patients with MS and NMOSD
[4]. These findings indicate that HMGB1
may be involved with inflammation in MS and NMOSD. Also, the
administration of anti-HMGB1 monoclonal antibodies ameliorated clinical
symptoms, CNS inflammation, demyelination, and serum IL-17 upregulation
in experimental autoimmune encephalomyelitis (EAE)
[11]. These findings suggest that HMGB1
may control autoimmune responses by stimulating the release of
inflammatory cytokines in MS. Recently, peroxiredoxins (PRXs), which are
intracellular antioxidant enzymes, attract attention as novel DAMPs.
Extracellular PRXs also induce the production of inflammatory cytokines
and triggers inflammation; the pro-inflammatory effects of PRXs are
reported to be stronger than that of HMGB1
[12]. Besides increasing inflammation,
PRXs was reported to affect the blood–brain barrier function
[13], which is another important factor
in the pathogenesis of MS and NMOSD [14].
We speculate that PRXs could be key players in the inflammatory response
of demyelinating CNS disorders, including MS and NMOSD, and could be a
future therapeutic target. However, the exact function of PRXs in the
pathogenesis of MS and NMOSD is not yet fully understood. The main aim
of this study is to determine whether PRXs are involved in promoting
inflammatory processes and affecting the blood–brain barrier function
in patients with MS and NMOSD.