Serum GFAP and neurofilament light as biomarkers of disease activity and disability in NMOSD

Watanabe, Mitsuru; Nakamura, Yuri; Michalak, Zuzanna; Isobe, Noriko; Barro, Christian; Leppert, David; Matsushita, Takuya; Hayashi, Fumie; Yamasaki, Ryo; Kühle, Jens; Kira, Jun‐ichi

doi:10.1212/wnl.0000000000008160

Cited by 146 publications

(207 citation statements)

References 45 publications

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“…However, currently there is still some uncertainty if GFAP autoimmunity is a primary disease process or a downstream effect of some forms of astrocytic injury 37. In the future, measuring GFAP in the serum may be a less invasive alternative to CSF measurements, as serum GFAP levels have been shown to be increased in NMOSD as well 18. An important consideration when talking about double-Ab-seronegative NMOSD diagnosis is the possibility of false-negative AQP4-Ab or MOG-Ab results.…”

Section: Discussionmentioning

confidence: 99%

“…Glial fibrillary acidic protein (GFAP), a part of the astrocyte cytoskeleton, is a very useful biomarker when investigating astrocytic damage 13. A very substantial increase in cerebrospinal fluid (CSF) GFAP levels during AQP4-Ab-seropositive NMOSD relapses has consistently been reported, and some reports also show low levels of GFAP in MOG-Ab-seropositive disease 4 6 7 14–18…”

Section: Introductionmentioning

confidence: 99%

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

Kleerekooper

Herbert

Kuiperij

et al. 2020

J Neurol Neurosurg Psychiatry

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ObjectiveTo 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.MethodsCerebrospinal 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).ResultsGFAP 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.ConclusionsOur 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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Kleerekooper

Herbert

Kuiperij

et al. 2020

J Neurol Neurosurg Psychiatry

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“…The 0.025% MWCNT-agarose scaffolds showed higher water retention than the others, demonstrating 0.025% wt MWCNTs were near to the optimum concentration between MWCNTs and agarose. Furthermore, the water-dispersed MWCNTs showed no impact on the expressions of neurofilament, which are neuron structural element [71,72]. This supports their application in peripheral nerve.…”

mentioning

confidence: 54%

Preparation of Multiwall Carbon Nanotubes Embedded Electroconductive Multi-Microchannel Scaffolds for Neuron Growth under Electrical Stimulation

Liu

Yushan

Alike

et al. 2020

BioMed Research International

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Objectives. To prepare the conductive MWCNT (multiwall carbon nanotube)-agarose scaffolds with multi-microchannel for neuron growth under electrical stimulation. Methods. The scaffolds were produced by gradient freeze and lyophilization methods. The synthesized materials were characterized by SEM and near-infrared spectroscopy, and their microstructure, swelling-deswelling, conductivity, biocompatibility, and shape memory behavior were measured. A three-dimensional culture model by implanting cells into scaffolds was built, and the behaviors of RSC96 cells on scaffolds under electrical stimulation were evaluated. Results. The addition of MWCNT did not affect the pore composition ratio and shape memory of agarose scaffolds, but 0.025% wt MWCNT in scaffolds improved the swelling ratio and water retention at the swelling equilibrium state. Though MWCNTs in high concentration had slight effect on proliferation of RSC96 cells and PC12 cells, there was no difference that the expressions of neurofilament of RSC96 cells on scaffolds with MWCNTs of different concentration. RSC96 cells arranged better along the longitudinal axis of scaffolds and showed better adhesion on both 0.025% MWCNT-agarose scaffolds and 0.05% MWCNT-agarose scaffolds compared to other scaffolds. Conclusions. Agarose scaffolds with MWCNTs possessed promising applicable prospect in peripheral nerve defects.

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“…Increased GFAP reflects astrocyte damage and death in AQP4-IgG + NMOSD [38,39]. It was not increased in AQP4-IgG seronegative NMOSD indicating that at least in a subset of these patients' disease mechanisms do not primarily target astrocytes.…”

Section: Molecular Markers In Aqp4-igg + Nmosdmentioning

confidence: 94%

Molecular markers in the CSF proteome differentiate neuroinflammatory diseases

Elkjaer¹,

Nawrocki²,

Kacprowski³

et al. 2020

Preprint

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Background: Multiple sclerosis (MS) is characterized by different degree of inflammatory and neurodegenerative features in the early relapsing vs. progressive subtypes. By using controls with different extent of inflammation vs. neurodegeneration, we examined the CSF proteome to identify molecular markers that differentiate between subtypes of MS. Gene expression of specific proteins were explored in MS brain lesions with diverse pathological background. Methods: (i) First, we compared the proteome by LC-MS/MS in 169 pooled CSF from MS subtypes to inflammatory/degenerative controls: AQP4-IgG-positive and AQP4-IgG-negative neuromyelitis optica spectrum disorder (NMOSD), Alzheimer’s disease (AD), and healthy controls. F-test based feature selection was used to cluster diseases and MS subtypes. (ii) Next, we selected 299 molecules by comprehensive statistics, and quantified them in the individual CSF samples. (iii) We also screened the genes of MS-specific CSF proteins in transcriptomes of 73 MS brain lesions with different pathology. Results: We identified 11 proteins that separated diseases, and 8 proteins that clustered MS subtypes. Secondary progressive (SP)MS had the most unique proteome characterized by upregulation of intrinsic pathway proteins of the coagulation pathway. SPMS also clustered far from NMOSD indicating less inflammatory pathways. Primary progressive (PP)MS was more similar to relapsing-remitting (RR)MS than SPMS. Quantification of 299 proteins in 170 individual CSF samples identified 5 molecules uniquely upregulated in MS subtypes and in AQP4-IgG-positive NMOSD, respectively. Chitinase-3-like protein 1 (CHI3L1) was upregulated in part of PPMS and remission CSF samples, and it was expressed by astrocytes in chronic active lesions. GFAP was upregulated in 70% of AQP4-IgG-positive NMOSD but only in 40% of AQP4-IgG-negative NMOSD. Conclusions: By the combination of untargeted and targeted quantitative analysis, we identified CSF molecular markers of axonal growth inhibition, lipid binding, and protein/lipid transport that differentiated between neuroinflammatory and neurodegenerative diseases, and also MS subtypes. The majority of them were expressed in MS brain lesions suggesting their origin from the brain tissue and not from the systemic compartment. Data suggest that the CSF proteome of SPMS is different from PPMS, and astrocyte damage may not be major pathology in part of the AQP4-IgG seronegative NMOSD.

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Serum GFAP and neurofilament light as biomarkers of disease activity and disability in NMOSD

Cited by 146 publications

References 45 publications

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

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

Preparation of Multiwall Carbon Nanotubes Embedded Electroconductive Multi-Microchannel Scaffolds for Neuron Growth under Electrical Stimulation

Molecular markers in the CSF proteome differentiate neuroinflammatory diseases

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