Recent studies showed that the
14-3-3 protein is detectable in the cerebrospinal fluid (CSF) of
prion-unrelated neurological diseases, such as
meningoencephalitis and
myelitis. To investigate the possible association between the amounts of the
14-3-3 protein in the CSF and the clinical severity of
multiple sclerosis (MS), its levels were determined by Western blot in the CSF of the patients with relapsing-remitting MS (RRMS) (n=10), secondary progressive MS (SPMS) (n=7), primary progressive MS (PPMS) (n=2), and non-MS inflammatory diseases of the CNS (n=5). The
14-3-3 protein was identified in seven CSF samples, including four patients with SPMS in acute relapse, one with SPMS in remission accompanied by fresh
cerebral infarction, one with RRMS in acute relapse, and one with human T-lymphotropic virus type I (
HTLV-I)-associated myelopathy. The patients positive for the CSF
14-3-3 protein immunoreactivity showed more severe disability and higher levels of
pleocytosis,
protein,
IgG, beta2-microglobulin, and
neuron-specific enolase in the CSF, compared with those negative for its immunoreactivity. Four of these patients exhibited extensive lesions distributed along multiple vertebral segments in the spinal cord on MRI. In contrast, none of the MS patients without an extensive involvement of the spinal cord showed the CSF
14-3-3 protein immunoreactivity. These results suggest that detection of the
14-3-3 protein in the CSF provides a marker for severe
inflammation-induced extensive damage of the central nervous system tissues responsible for poor therapeutic responses and irreversible neurological deficits in MS.