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Cited by 512Autoimmune Neurological Disorders and TreatmentsPeripheral Neuropathies and DisordersMyasthenia Gravis and Thymoma

Neuronal autoantigens—pathogenesis, associated disorders and antibody testing

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Lancaster, Eric, Dalmau, Josep·2012·Nature Reviews Neurology
DOI 10.1038/nrneurol.2012.99PMC PMC3718498
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Abstract

The discovery of disorders that are associated with antibodies to neuronal cell-surface proteins has led to a paradigm shift in our understanding of CNS autoimmunity. These disorders can occur in patients with or without cancer-often children or young adults who develop psychosis, catatonic or autistic features, memory problems, abnormal movements, or seizures that were previously considered idiopathic. The autoantigens in such cases have crucial roles in synaptic transmission, plasticity and peripheral nerve excitability. Patients can be comatose or encephalopathic for months and yet fully recover with supportive care and immunotherapy. By contrast, disorders in which the antibodies target intracellular antigens, and in which T-cell-mediated irreversible neuronal degeneration occurs, show a considerably poorer response to treatment. In this article, we review the various targets of neuronal antibodies, focusing predominantly on autoantigens located on the cell surface or synapses-namely, N-methyl-D-aspartate receptors, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, γ-aminobutyric acid receptors, leucine-rich glioma-inactivated protein 1, contactin-associated protein-like 2, and metabotropic glutamate receptors. We also provide an algorithm to identify and assess antibodies that bind to cell-surface and synaptic antigens.

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  • The discovery of anti-NMDAR encephalitis has changed the diagnostic and treatment approach to several neurologic and psychiatric disorders, and has led to the identification of an expanding group of autoimmune encephalitis related to antibodies against synaptic proteins.

    “The discovery of anti-NMDAR encephalitis has changed the diagnostic and treatment approach to several neurologic and psychiatric disorders, and has led to the identification of an expanding group of autoimmune encephalitis related to antibodies against synaptic proteins.19”

    From Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study (2013) · cites this paper as [19]

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Authors
Lancaster, E., & Dalmau, J.
Affiliations
  • University of Pennsylvania (US)
  • Institució Catalana de Recerca i Estudis Avançats (ES)
Corresponding author
Lancaster, Eric
ORCID
Venue
Nature Reviews Neurology
Publisher
Springer Science and Business Media LLC
Published
2012-06-19
Volume
8
Issue
7
Pages
380-390
ISSN
  • 1759-4758 (ISSN-L)
  • 1759-4766
DOI
10.1038/nrneurol.2012.99
PMC
PMC3718498
OpenAlex
W1980325803
Cited by
512
References
3
Citations by year
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FWCI
6.79
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Reviews Neurology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Dana Foundation
  • National Organization for Rare Disorders
  • Fundació la Marató de TV3
  • National Institutes of Health
  • National Institute of Mental Health (R01MH094741)
  • National Cancer Institute (R01CA089054, R56CA089054, R01CA107192)
  • National Institute of Neurological Disorders and Stroke (R01NS077851)
Topics
  • Health Sciences › Medicine › Neurology › Autoimmune Neurological Disorders and Treatments
  • Health Sciences › Medicine › Neurology › Peripheral Neuropathies and Disorders
  • Health Sciences › Medicine › Neurology › Myasthenia Gravis and Thymoma
Keywords
neuronal autoantibodies, autoantigens, central nervous system autoimmunity, NMDA receptor antibodies, AMPA receptor antibodies, CASPR2 antibodies, neurotransmitter receptors, synaptic transmission, antibody detection, autoimmune encephalitis, immunotherapy, seizures
MeSH terms
Algorithms, Antibodies, Autoantigens, Humans, Membrane Proteins, Models, Biological, Neurons, Protein Binding, Synapses, Autoimmune Diseases of the Nervous System

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