TY - JOUR
T1 - CSF levels of glutamine synthetase and GFAP to explore astrocytic damage in seronegative NMOSD
AU - Kleerekooper, Iris
AU - Herbert, Megan K.
AU - Kuiperij, H. Bea
AU - Sato, Douglas Kazutoshi
AU - Fujihara, Kazuo
AU - Callegaro, Dagoberto
AU - Marignier, Romain
AU - Saiz, Albert
AU - Senel, Makbule
AU - Tumani, Hayrettin
AU - De Jong, Brigit A.
AU - Trip, S. Anand
AU - Nakashima, Ichiro
AU - Verbeek, Marcel M.
AU - Petzold, Axel
PY - 2020/6/1
Y1 - 2020/6/1
N2 - Objective To explore levels of astrocytopathy in neuromyelitis optica spectrum disorder (NMOSD) by measuring levels of the astrocytic enzyme glutamine synthetase (GS) and glial fibrillary acidic protein (GFAP), an established astrocytic biomarker known to be associated with disease activity in multiple sclerosis. Methods Cerebrospinal fluid concentrations of GS and GFAP were measured by ELISA in patients with NMOSD (n=39, 28 aquaporin-4 (AQP4)-Ab-seropositive, 3 double-Ab-seronegative, 4 myelin oligodendrocyte glycoprotein (MOG)-Ab-seropositive and 4 AQP4-Ab-seronegative with unknown MOG-Ab-serostatus), multiple sclerosis (MS) (n=69), optic neuritis (n=5) and non-neurological controls (n=37). Results GFAP and GS concentrations differed significantly across groups (both p<0.001), showing a similar pattern of elevation in patients with AQP4-Ab-seropositive NMOSD. GS and GFAP were significantly correlated, particularly in patients with AQP4-Ab-seropositive NMOSD (r s =0.70, p<0.001). Interestingly, GFAP levels in some patients with double-Ab-seronegative NMOSD were markedly increased. Conclusions Our data indicate astrocytic injury occurs in some patients with double-Ab-seronegative NMOSD, which hints at the possible existence of yet undiscovered astrocytic autoimmune targets. We hypothesise that elevated GS and GFAP levels could identify those double-Ab-seronegative patients suitable to undergo in-depth autoimmune screening for astrocytic antibodies.
AB - Objective To explore levels of astrocytopathy in neuromyelitis optica spectrum disorder (NMOSD) by measuring levels of the astrocytic enzyme glutamine synthetase (GS) and glial fibrillary acidic protein (GFAP), an established astrocytic biomarker known to be associated with disease activity in multiple sclerosis. Methods Cerebrospinal fluid concentrations of GS and GFAP were measured by ELISA in patients with NMOSD (n=39, 28 aquaporin-4 (AQP4)-Ab-seropositive, 3 double-Ab-seronegative, 4 myelin oligodendrocyte glycoprotein (MOG)-Ab-seropositive and 4 AQP4-Ab-seronegative with unknown MOG-Ab-serostatus), multiple sclerosis (MS) (n=69), optic neuritis (n=5) and non-neurological controls (n=37). Results GFAP and GS concentrations differed significantly across groups (both p<0.001), showing a similar pattern of elevation in patients with AQP4-Ab-seropositive NMOSD. GS and GFAP were significantly correlated, particularly in patients with AQP4-Ab-seropositive NMOSD (r s =0.70, p<0.001). Interestingly, GFAP levels in some patients with double-Ab-seronegative NMOSD were markedly increased. Conclusions Our data indicate astrocytic injury occurs in some patients with double-Ab-seronegative NMOSD, which hints at the possible existence of yet undiscovered astrocytic autoimmune targets. We hypothesise that elevated GS and GFAP levels could identify those double-Ab-seronegative patients suitable to undergo in-depth autoimmune screening for astrocytic antibodies.
UR - http://www.scopus.com/inward/record.url?scp=85082514526&partnerID=8YFLogxK
U2 - https://doi.org/10.1136/jnnp-2019-322286
DO - https://doi.org/10.1136/jnnp-2019-322286
M3 - Article
C2 - 32217788
SN - 0022-3050
VL - 91
SP - 605
EP - 611
JO - Journal of neurology, neurosurgery, and psychiatry
JF - Journal of neurology, neurosurgery, and psychiatry
IS - 6
M1 - 322286
ER -