Evidence map›Paper›PMID 39141878›Full record

ArticleNeurology(R) neuroimmunology & neuroinflammation2024

LGI1 Autoantibodies Enhance Synaptic Transmission by Presynaptic K

Andreas Ritzau-Jost, Felix Gsell, Josefine Sell, Stefan Sachs, Jacqueline Montanaro, Toni Kirmann, Sebastian Maaß, Sarosh R Irani, Christian Werner, Christian Geis and 3 more

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Article in Neurology(R) neuroimmunology & neuroinflammation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
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

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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

5 citing papers in PubMed.

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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

13 authors.

Andreas Ritzau-JostFrom the Carl-Ludwig-Institute of Physiology (A.R.-J., F.G., T.K., S.M., S.H.), Faculty of Medicine, Leipzig University; Section Translational Neuroimmunology (J.S., C.G.), Department of Neurology, Jena University Hospital; Department of Biotechnology and Biophysics (S.S., C.W., M.S.), University of Würzburg, Biocenter, Germany; Institute of Science and Technology Austria (ISTA) (J.M., R.S.), Klosterneuburg, Austria; Oxford Autoimmune Neurology Group (S.R.I.), Nuffield Department of Clinical Neurosciences, University of Oxford, ; Department of Neurology (S.R.I.), John Radcliffe Hospital, Oxford University Hospitals, United Kingdom; and Departments of Neurology and Neurosciences (S.R.I.), Mayo Clinic Jacksonville, FL.
Felix GsellFrom the Carl-Ludwig-Institute of Physiology (A.R.-J., F.G., T.K., S.M., S.H.), Faculty of Medicine, Leipzig University; Section Translational Neuroimmunology (J.S., C.G.), Department of Neurology, Jena University Hospital; Department of Biotechnology and Biophysics (S.S., C.W., M.S.), University of Würzburg, Biocenter, Germany; Institute of Science and Technology Austria (ISTA) (J.M., R.S.), Klosterneuburg, Austria; Oxford Autoimmune Neurology Group (S.R.I.), Nuffield Department of Clinical Neurosciences, University of Oxford, ; Department of Neurology (S.R.I.), John Radcliffe Hospital, Oxford University Hospitals, United Kingdom; and Departments of Neurology and Neurosciences (S.R.I.), Mayo Clinic Jacksonville, FL.
Josefine SellFrom the Carl-Ludwig-Institute of Physiology (A.R.-J., F.G., T.K., S.M., S.H.), Faculty of Medicine, Leipzig University; Section Translational Neuroimmunology (J.S., C.G.), Department of Neurology, Jena University Hospital; Department of Biotechnology and Biophysics (S.S., C.W., M.S.), University of Würzburg, Biocenter, Germany; Institute of Science and Technology Austria (ISTA) (J.M., R.S.), Klosterneuburg, Austria; Oxford Autoimmune Neurology Group (S.R.I.), Nuffield Department of Clinical Neurosciences, University of Oxford, ; Department of Neurology (S.R.I.), John Radcliffe Hospital, Oxford University Hospitals, United Kingdom; and Departments of Neurology and Neurosciences (S.R.I.), Mayo Clinic Jacksonville, FL.
Stefan SachsFrom the Carl-Ludwig-Institute of Physiology (A.R.-J., F.G., T.K., S.M., S.H.), Faculty of Medicine, Leipzig University; Section Translational Neuroimmunology (J.S., C.G.), Department of Neurology, Jena University Hospital; Department of Biotechnology and Biophysics (S.S., C.W., M.S.), University of Würzburg, Biocenter, Germany; Institute of Science and Technology Austria (ISTA) (J.M., R.S.), Klosterneuburg, Austria; Oxford Autoimmune Neurology Group (S.R.I.), Nuffield Department of Clinical Neurosciences, University of Oxford, ; Department of Neurology (S.R.I.), John Radcliffe Hospital, Oxford University Hospitals, United Kingdom; and Departments of Neurology and Neurosciences (S.R.I.), Mayo Clinic Jacksonville, FL.
Jacqueline MontanaroFrom the Carl-Ludwig-Institute of Physiology (A.R.-J., F.G., T.K., S.M., S.H.), Faculty of Medicine, Leipzig University; Section Translational Neuroimmunology (J.S., C.G.), Department of Neurology, Jena University Hospital; Department of Biotechnology and Biophysics (S.S., C.W., M.S.), University of Würzburg, Biocenter, Germany; Institute of Science and Technology Austria (ISTA) (J.M., R.S.), Klosterneuburg, Austria; Oxford Autoimmune Neurology Group (S.R.I.), Nuffield Department of Clinical Neurosciences, University of Oxford, ; Department of Neurology (S.R.I.), John Radcliffe Hospital, Oxford University Hospitals, United Kingdom; and Departments of Neurology and Neurosciences (S.R.I.), Mayo Clinic Jacksonville, FL.
Toni KirmannFrom the Carl-Ludwig-Institute of Physiology (A.R.-J., F.G., T.K., S.M., S.H.), Faculty of Medicine, Leipzig University; Section Translational Neuroimmunology (J.S., C.G.), Department of Neurology, Jena University Hospital; Department of Biotechnology and Biophysics (S.S., C.W., M.S.), University of Würzburg, Biocenter, Germany; Institute of Science and Technology Austria (ISTA) (J.M., R.S.), Klosterneuburg, Austria; Oxford Autoimmune Neurology Group (S.R.I.), Nuffield Department of Clinical Neurosciences, University of Oxford, ; Department of Neurology (S.R.I.), John Radcliffe Hospital, Oxford University Hospitals, United Kingdom; and Departments of Neurology and Neurosciences (S.R.I.), Mayo Clinic Jacksonville, FL.
Sebastian MaaßFrom the Carl-Ludwig-Institute of Physiology (A.R.-J., F.G., T.K., S.M., S.H.), Faculty of Medicine, Leipzig University; Section Translational Neuroimmunology (J.S., C.G.), Department of Neurology, Jena University Hospital; Department of Biotechnology and Biophysics (S.S., C.W., M.S.), University of Würzburg, Biocenter, Germany; Institute of Science and Technology Austria (ISTA) (J.M., R.S.), Klosterneuburg, Austria; Oxford Autoimmune Neurology Group (S.R.I.), Nuffield Department of Clinical Neurosciences, University of Oxford, ; Department of Neurology (S.R.I.), John Radcliffe Hospital, Oxford University Hospitals, United Kingdom; and Departments of Neurology and Neurosciences (S.R.I.), Mayo Clinic Jacksonville, FL.
Sarosh R IraniFrom the Carl-Ludwig-Institute of Physiology (A.R.-J., F.G., T.K., S.M., S.H.), Faculty of Medicine, Leipzig University; Section Translational Neuroimmunology (J.S., C.G.), Department of Neurology, Jena University Hospital; Department of Biotechnology and Biophysics (S.S., C.W., M.S.), University of Würzburg, Biocenter, Germany; Institute of Science and Technology Austria (ISTA) (J.M., R.S.), Klosterneuburg, Austria; Oxford Autoimmune Neurology Group (S.R.I.), Nuffield Department of Clinical Neurosciences, University of Oxford, ; Department of Neurology (S.R.I.), John Radcliffe Hospital, Oxford University Hospitals, United Kingdom; and Departments of Neurology and Neurosciences (S.R.I.), Mayo Clinic Jacksonville, FL.ORCID 0000-0002-7667-9748
Christian WernerFrom the Carl-Ludwig-Institute of Physiology (A.R.-J., F.G., T.K., S.M., S.H.), Faculty of Medicine, Leipzig University; Section Translational Neuroimmunology (J.S., C.G.), Department of Neurology, Jena University Hospital; Department of Biotechnology and Biophysics (S.S., C.W., M.S.), University of Würzburg, Biocenter, Germany; Institute of Science and Technology Austria (ISTA) (J.M., R.S.), Klosterneuburg, Austria; Oxford Autoimmune Neurology Group (S.R.I.), Nuffield Department of Clinical Neurosciences, University of Oxford, ; Department of Neurology (S.R.I.), John Radcliffe Hospital, Oxford University Hospitals, United Kingdom; and Departments of Neurology and Neurosciences (S.R.I.), Mayo Clinic Jacksonville, FL.
Christian GeisFrom the Carl-Ludwig-Institute of Physiology (A.R.-J., F.G., T.K., S.M., S.H.), Faculty of Medicine, Leipzig University; Section Translational Neuroimmunology (J.S., C.G.), Department of Neurology, Jena University Hospital; Department of Biotechnology and Biophysics (S.S., C.W., M.S.), University of Würzburg, Biocenter, Germany; Institute of Science and Technology Austria (ISTA) (J.M., R.S.), Klosterneuburg, Austria; Oxford Autoimmune Neurology Group (S.R.I.), Nuffield Department of Clinical Neurosciences, University of Oxford, ; Department of Neurology (S.R.I.), John Radcliffe Hospital, Oxford University Hospitals, United Kingdom; and Departments of Neurology and Neurosciences (S.R.I.), Mayo Clinic Jacksonville, FL.ORCID 0000-0002-9859-581X
Markus SauerFrom the Carl-Ludwig-Institute of Physiology (A.R.-J., F.G., T.K., S.M., S.H.), Faculty of Medicine, Leipzig University; Section Translational Neuroimmunology (J.S., C.G.), Department of Neurology, Jena University Hospital; Department of Biotechnology and Biophysics (S.S., C.W., M.S.), University of Würzburg, Biocenter, Germany; Institute of Science and Technology Austria (ISTA) (J.M., R.S.), Klosterneuburg, Austria; Oxford Autoimmune Neurology Group (S.R.I.), Nuffield Department of Clinical Neurosciences, University of Oxford, ; Department of Neurology (S.R.I.), John Radcliffe Hospital, Oxford University Hospitals, United Kingdom; and Departments of Neurology and Neurosciences (S.R.I.), Mayo Clinic Jacksonville, FL.
Ryuichi ShigemotoFrom the Carl-Ludwig-Institute of Physiology (A.R.-J., F.G., T.K., S.M., S.H.), Faculty of Medicine, Leipzig University; Section Translational Neuroimmunology (J.S., C.G.), Department of Neurology, Jena University Hospital; Department of Biotechnology and Biophysics (S.S., C.W., M.S.), University of Würzburg, Biocenter, Germany; Institute of Science and Technology Austria (ISTA) (J.M., R.S.), Klosterneuburg, Austria; Oxford Autoimmune Neurology Group (S.R.I.), Nuffield Department of Clinical Neurosciences, University of Oxford, ; Department of Neurology (S.R.I.), John Radcliffe Hospital, Oxford University Hospitals, United Kingdom; and Departments of Neurology and Neurosciences (S.R.I.), Mayo Clinic Jacksonville, FL.
Stefan HallermannFrom the Carl-Ludwig-Institute of Physiology (A.R.-J., F.G., T.K., S.M., S.H.), Faculty of Medicine, Leipzig University; Section Translational Neuroimmunology (J.S., C.G.), Department of Neurology, Jena University Hospital; Department of Biotechnology and Biophysics (S.S., C.W., M.S.), University of Würzburg, Biocenter, Germany; Institute of Science and Technology Austria (ISTA) (J.M., R.S.), Klosterneuburg, Austria; Oxford Autoimmune Neurology Group (S.R.I.), Nuffield Department of Clinical Neurosciences, University of Oxford, ; Department of Neurology (S.R.I.), John Radcliffe Hospital, Oxford University Hospitals, United Kingdom; and Departments of Neurology and Neurosciences (S.R.I.), Mayo Clinic Jacksonville, FL.ORCID 0000-0001-9376-7048

Funding

Medical Research Council MR/V007173/1
6 · The paper itself

Abstract

BACKGROUND AND

objectivesAutoantibodies against the protein leucine-rich glioma inactivated 1 (LGI1) cause the most common subtype of autoimmune encephalitis with predominant involvement of the limbic system, associated with seizures and memory deficits. LGI1 and its receptor ADAM22 are part of a transsynaptic protein complex that includes several proteins involved in presynaptic neurotransmitter release and postsynaptic glutamate sensing. Autoantibodies against LGI1 increase excitatory synaptic strength, but studies that genetically disrupt the LGI1-ADAM22 complex report a reduction in postsynaptic glutamate receptor-mediated responses. Thus, the mechanisms underlying the increased synaptic strength induced by LGI1 autoantibodies remain elusive, and the contributions of presynaptic molecules to the LGI1-transsynaptic complex remain unclear. We therefore investigated the presynaptic mechanisms that mediate autoantibody-induced synaptic strengthening.

methodsWe studied the effects of patient-derived purified polyclonal LGI1 autoantibodies on synaptic structure and function by combining direct patch-clamp recordings from presynaptic boutons and somata of hippocampal neurons with super-resolution light and electron microscopy of hippocampal cultures and brain slices. We also identified the protein domain mediating the presynaptic effect using domain-specific patient-derived monoclonal antibodies.

resultsLGI1 autoantibodies dose-dependently increased short-term depression during high-frequency transmission, consistent with increased release probability. The increased neurotransmission was not related to presynaptic calcium channels because presynaptic Ca DISCUSSION: Our results indicate that LGI1 autoantibodies reduce the density of both K

Indexed as

Action PotentialsAutoantibodiesIntracellular Signaling Peptides and ProteinsPresynaptic TerminalsSynaptic TransmissionAnimalsCells, CulturedHippocampusHumansKv1.1 Potassium ChannelMaleProteinsRatsAutoantibodiesIntracellular Signaling Peptides and ProteinsKv1.1 Potassium ChannelLGI1 protein, humanProteins

Identifiers

PMID39141878
PMCPMC11379440

What Socratic holds

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