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Cited by 143Autoimmune Neurological Disorders and TreatmentsPeripheral Neuropathies and DisordersNeuroscience and Neuropharmacology Research

IgA NMDA receptor antibodies are markers of synaptic immunity in slow cognitive impairment

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Prüss, H., Höltje, M., Maier, N., Gomez, A., Buchert, R., Harms, L., Ahnert-Hilger, G., Schmitz, D. +9 more·2012·Neurology
DOI 10.1212/wnl.0b013e318258300dPMC PMC3359581
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Abstract

OBJECTIVE: To report that antibodies to synaptic proteins may occur in association with slow, progressive cognitive decline. METHODS: A total of 24 patients with progressive cognitive dysfunction of unclear etiology were examined for onconeuronal and synaptic receptor antibodies. The effect of serum was examined in cultures of dissociated mouse hippocampal neurons. RESULTS: Seven patients had immunoglobulin A (IgA), but no immunoglobulin G (IgG), antibodies against NMDA receptor (NMDAR). Anti-NMDAR IgA positive patients' serum, but not serum from control individuals, caused dramatic decrease of the levels of NMDAR and other synaptic proteins in neurons, along with prominent changes in NMDAR-mediated currents. These effects correlated with the titer of IgA NMDAR antibodies and were reversed after removing patients' serum from the culture media. When available, comprehensive clinical assessment and brain metabolic imaging showed neurologic improvement after immunotherapy. CONCLUSIONS: A subset of patients with slowly progressive cognitive impairment has an underlying synaptic autoimmunity that decreases the density of NMDAR and other synaptic proteins, and alters synaptic currents. This autoimmunity can be demonstrated examining patients' serum and CSF for NMDAR IgA antibodies, identifying possible candidates for immunotherapy.

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  • Rapidly progressive alterations of memory, behavior, cognition, and psychosis previously thought to be idiopathic or viral-induced are now known to be autoimmune.

    “Rapidly progressive alterations of memory, behavior, cognition, and psychosis previously thought to be idiopathic or viral-induced are now known to be autoimmune.20-23”

    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 [22]

    The Discussion says synaptic autoimmunity can cause acute, severe changes in memory, behavior, and cognition, and the Index patient section describes delusions and hallucinations. But this paper primarily studies slowly progressive impairment; the Clinical course section says none of its seven patients had acute symptoms resembling classic anti-NMDAR encephalitis. Our copy does not establish that these conditions were previously thought to be viral-induced. (LLM, conf=0.88)

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Cites

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Authors
Prüss, H., Höltje, M., Maier, N., Gomez, A., Buchert, R., Harms, L., Ahnert-Hilger, G., Schmitz, D., Terborg, C., Kopp, U., Klingbeil, C., Probst, C., Kohler, S., Schwab, J. M., Stoecker, W., Dalmau, J., & Wandinger, K. P.
Affiliations
  • German Center for Neurodegenerative Diseases (DE)
  • Harvard University (US)
  • From the Department of Neurology (H.P., L.H., U.K., S.K., J.M.S.), Institute for Integrative Neuroanatomy (M.H., G.A.-H.), Neuroscience Research Center (N.M., D.S.), Department of Psychiatry (A.G.), and Department of Nuclear Medicine (R.B.), Charité University Medicine Berlin, Berlin; Cluster of Excellence (D.S.), NeuroCure and Bernstein Center for Computational Neuroscience Berlin (BCCNB), Berlin; DZNE–German Center for Neurodegenerative Diseases (D.S.), Berlin; Department of Neurology (C.T.),...
ORCID
Venue
Neurology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2012-05-29
Volume
78
Issue
22
Pages
1743-1753
ISSN
  • 0028-3878 (ISSN-L)
  • 1526-632X
DOI
10.1212/wnl.0b013e318258300d
PMC
PMC3359581
OpenAlex
W2120325372
Cited by
143
References
3
Citations by year
2026: 5 · 2025: 4 · 2024: 3 · 2023: 8 · 2022: 11 · 2021: 4 · 2020: 6 · 2019: 11 · 2018: 9 · 2017: 11 · 2016: 13 · 2015: 11 · 2014: 20 · 2013: 16 · 2012: 11
FWCI
11.42
Type
journal article
Language
en
Open access
Locations
  • Neurology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
  • DZNE Pub (submittedVersion)
Funders
  • Deutscher Akademischer Austauschdienst
  • Deutsche Forschungsgemeinschaft (EXC257, SFB618)
  • Bundesministerium für Bildung und Forschung
  • National Institutes of Health
  • National Cancer Institute (R01CA89054-06A2, R01CA089054, R01CA107192)
Topics
  • Health Sciences › Medicine › Neurology › Autoimmune Neurological Disorders and Treatments
  • Health Sciences › Medicine › Neurology › Peripheral Neuropathies and Disorders
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
NMDA receptor antibodies, IgA autoantibodies, NMDA receptor, synaptic proteins, hippocampal neurons, immunotherapy, cerebrospinal fluid biomarkers, autoimmune encephalitis
MeSH terms
Rituximab, Adrenal Cortex Hormones, Aged, Alzheimer Disease, Atrophy, Cognition Disorders, Cyclophosphamide, Electrophysiology, Female, Frontal Lobe, Hippocampus, Humans, Immunoglobulin A, Immunohistochemistry, Immunotherapy, Magnetic Resonance Imaging, Neurons, Plasma Exchange, Synapses, Temporal Lobe, Blotting, Western, Biomarkers, Autoimmunity, Receptors, N-Methyl-D-Aspartate, Treatment Outcome, Disease Progression, Radiopharmaceuticals, Fluorodeoxyglucose F18, Lewy Body Disease, Positron-Emission Tomography, Antibodies, Monoclonal, Murine-Derived

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