CSF levels of glutamine synthetase and GFAP to explore astrocytic damage in seronegative NMOSD

Iris Kleerekooper*, Megan K. Herbert, H. Bea Kuiperij, Douglas Kazutoshi Sato, Kazuo Fujihara, Dagoberto Callegaro, Romain Marignier, Albert Saiz, Makbule Senel, Hayrettin Tumani, Brigit A. De Jong, S. Anand Trip, Ichiro Nakashima, Marcel M. Verbeek, Axel Petzold

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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 (rs=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.

Original languageEnglish
Article number322286
Number of pages7
JournalJournal of Neurology, Neurosurgery and Psychiatry
Issue number6
Publication statusAccepted/In press - 1 Jan 2020

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Kleerekooper, I., Herbert, M. K., Kuiperij, H. B., Sato, D. K., Fujihara, K., Callegaro, D., ... Petzold, A. (Accepted/In press). CSF levels of glutamine synthetase and GFAP to explore astrocytic damage in seronegative NMOSD. Journal of Neurology, Neurosurgery and Psychiatry, 91(6), [322286]. https://doi.org/10.1136/jnnp-2019-322286