Evidence map›Paper›PMID 25542977›Full record

ArticleExperimental neurology2015

The intrinsic pathogenic role of autoantibodies to aquaporin 4 mediating spinal cord disease in a rat passive-transfer model.

Christian Geis, Christian Ritter, Christoph Ruschil, Andreas Weishaupt, Benedikt Grünewald, Guido Stoll, Trygve Holmoy, Tatsuro Misu, Kazuo Fujihara, Bernhard Hemmer and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Experimental neurology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
4.2field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

36 citing papers in PubMed, 59 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 7 institutions in 4 countries.

Christian GeisDepartment of Neurology and Clinical Research Group for Multiple Sclerosis and Neuroimmunology, University of Würzburg, 97080 Würzburg, Germany; Hans Berger Department of Neurology, Jena University Hospital, 07747 Jena, Germany; The Integrated Research and Treatment Center for Sepsis Control and Care (CSCC), Jena University Hospital, 07747 Jena, Germany. Electronic address: christian.geis@med.uni-jena.de.
Christian RitterDepartment of Neurology and Clinical Research Group for Multiple Sclerosis and Neuroimmunology, University of Würzburg, 97080 Würzburg, Germany.
Christoph RuschilDepartment of Neurology and Clinical Research Group for Multiple Sclerosis and Neuroimmunology, University of Würzburg, 97080 Würzburg, Germany.
Andreas WeishauptDepartment of Neurology and Clinical Research Group for Multiple Sclerosis and Neuroimmunology, University of Würzburg, 97080 Würzburg, Germany.
Benedikt GrünewaldDepartment of Neurology and Clinical Research Group for Multiple Sclerosis and Neuroimmunology, University of Würzburg, 97080 Würzburg, Germany; Hans Berger Department of Neurology, Jena University Hospital, 07747 Jena, Germany; The Integrated Research and Treatment Center for Sepsis Control and Care (CSCC), Jena University Hospital, 07747 Jena, Germany.
Guido StollDepartment of Neurology and Clinical Research Group for Multiple Sclerosis and Neuroimmunology, University of Würzburg, 97080 Würzburg, Germany.
Trygve HolmoyDepartment of Neurology, Akershus University Hospital and Institute of Clinical Medicine, University of Oslo, 0318 Oslo, Norway.
Tatsuro MisuDepartment of Multiple Sclerosis Therapeutics and Neurology, Tohoku University Graduate School of Medicine, Sendai, 980-8577 Japan.
Kazuo FujiharaDepartment of Multiple Sclerosis Therapeutics and Neurology, Tohoku University Graduate School of Medicine, Sendai, 980-8577 Japan.
Bernhard HemmerKlinikum rechts der Isar, Technische Universität, 81675 Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), 81675 Munich, Germany.
Christine StadelmannInstitute of Neuropathology, University Medical Center Göttingen, 37099 Göttingen, Germany.
Jeffrey L BennettDepartments of Neurology and Ophthalmology, University of Colorado Denver, Aurora, CO 80045, USA.
Claudia SommerDepartment of Neurology and Clinical Research Group for Multiple Sclerosis and Neuroimmunology, University of Würzburg, 97080 Würzburg, Germany.
Klaus V ToykaDepartment of Neurology and Clinical Research Group for Multiple Sclerosis and Neuroimmunology, University of Würzburg, 97080 Würzburg, Germany.
University of Würzburg · DETohoku University · JPJena University Hospital · DEKlinikum rechts der Isar · DEUniversitätsmedizin Göttingen · DEUniversity of Colorado Denver · USUniversity of Oslo · NO

Funding

Humoral Immunity, Astrocyte Injury, and Demyelination in Neuromyelitis OpticaR01EY022936 · NEI · UNIVERSITY OF COLORADO DENVER · PI BENNETT, JEFFREY L · 2013 to 2022
$3.8M
NEI NIH HHS R01 EY022936
6 · The paper itself

Abstract

Neuromyelitis optica (NMO) is causally linked to autoantibodies (ABs) against aquaporin 4 (AQP4). Here, we focused on the pathogenic effects exclusively mediated by human ABs to AQP4 in vivo. We performed cell-free intrathecal (i.th.) passive transfer experiments in Lewis rats using purified patient NMO immunoglobulin G (IgG) and various recombinant human anti-AQP4 IgG-ABs via implanted i.th. catheters. Repetitive application of patient NMO IgG fractions and of recombinant human anti-AQP4 ABs induced signs of spinal cord disease. Magnetic resonance imaging (MRI) revealed longitudinal spinal cord lesions at the site of application of anti-AQP4 IgG. Somatosensory evoked potential amplitudes were reduced in symptomatic animals corroborating the observed functional impairment. Spinal cord histology showed specific IgG deposition in the grey and white matter in the affected areas. We did not find inflammatory cell infiltration nor activation of complement in spinal cord areas of immunoglobulin deposition. Moreover, destructive lesions showing axon or myelin damage and loss of astrocytes and oligodendrocytes were all absent. Immunoreactivity to AQP4 and to the excitatory amino acid transporter 2 (EAAT2) was markedly reduced whereas immunoreactivity to the astrocytic marker glial fibrillary acid protein (GFAP) was preserved. The expression of the NMDA-receptor NR1 subunit was downregulated in areas of IgG deposition possibly induced by sustained glutamatergic overexcitation. Disease signs and histopathology were reversible within weeks after stopping injections. We conclude that in vivo application of ABs directed at AQP 4 can induce a reversible spinal cord disease in recipient rats by inducing distinct histopathological abnormalities. These findings may be the experimental correlate of "penumbra-like" lesions recently reported in NMO patients adjacent to effector-mediated tissue damage.

Indexed as

Disease Models, AnimalAnimalsAquaporin 4AutoantibodiesFemaleHumansImmunization, PassiveInjections, SpinalNeuromyelitis OpticaRatsRats, Inbred LewSpinal Cord DiseasesAqp4 protein, ratAquaporin 4AutoantibodiesAquaporin 4AstrocyteEAAT2Intrathecal passive transferNeuromyelitis opticaNMDA receptor

Identifiers

PMID25542977
PMCPMC4382207
OpenAlexW1984664516

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.