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Record W3013582179 · doi:10.1136/jnnp-2019-322286

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

2020· article· en· W3013582179 on OpenAlexfundno aff
Iris Kleerekooper, Megan K. Herbert, H. Bea Kuiperij, Douglas Kazutoshi Sato, Kazuo Fujihara, Dagoberto Callegaro, Romain Marignier, Albert Saiz, Makbule Şenel, Hayrettin Tumani, Brigit A. de Jong, S. Anand Trip, Ichiro Nakashima, Marcel M. Verbeek, Axel Petzold

Bibliographic record

VenueJournal of Neurology Neurosurgery & Psychiatry · 2020
Typearticle
Languageen
FieldMedicine
TopicMultiple Sclerosis Research Studies
Canadian institutionsnot available
FundersSanofi GenzymeOno PharmaceuticalAlzheimer NederlandJapan Society for the Promotion of ScienceHeidelberg EngineeringUniversität UlmChugai PharmaceuticalMitsubishi Tanabe Pharma CorporationHospices Civils de LyonMinistry of Education, Science and TechnologyZonMwWeston Brain InstituteFundació la Marató de TV3Teijin PharmaNational Institute for Health and Care ResearchTeva Pharmaceutical IndustriesBundesministerium für Bildung und ForschungGemeinnützige Hertie-StiftungMylanCelgeneBiogenUniversity College LondonSanofi
KeywordsNeuromyelitis opticaGlial fibrillary acidic proteinGlutamine synthetaseMultiple sclerosisCerebrospinal fluidMyelin oligodendrocyte glycoproteinAstrocyteOptic neuritisMedicinePathologyAquaporin 4ImmunologyInternal medicineBiologyGlutamineImmunohistochemistryCentral nervous systemBiochemistryExperimental autoimmune encephalomyelitis

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.003

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.101
GPT teacher head0.332
Teacher spread0.231 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

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Citations36
Published2020
Admission routes1
Has abstractyes

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