N‐methyl‐ D ‐aspartate receptor antibodies in herpes simplex encephalitis
Open accessAbstract
Objective: To determine the presence and kinetics of antibodies against synaptic proteins in patients with herpes simplex virus encephalitis (HSE). Methods: Retrospective analysis of 44 patients with polymerase chain reaction‐proven HSE for the presence of a large panel of onconeuronal and synaptic receptor antibodies. The effect of patients' serum was studied in cultures of primary mouse hippocampal neurons. Results: N‐Methyl‐ D ‐aspartate receptor (NMDAR) antibodies of the immunoglobulin (Ig) subtypes IgA, IgG, or IgM were detected in 13 of 44 patients (30%) in the course of HSE, suggesting secondary autoimmune mechanisms. NMDAR antibodies were often present at hospital admission, but in some patients developed after the first week of HSE. Antibody‐positive sera resulted in downregulation of synaptic marker proteins in hippocampal neurons. Interpretation: Some patients with HSE develop IgA, IgG, or IgM autoantibodies against NMDAR. Sera from these patients alter the density of neuronal synaptic markers, suggesting a potential pathogenic disease‐modifying effect. These findings have implications for the understanding of autoimmunity in infectious diseases, and prospective studies should reveal whether the subgroup of patients with HSE and NMDAR antibodies may benefit from immunotherapy. ANN NEUROL 2012;72:902–911
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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 [23]
The Abstract’s Interpretation and the Discussion report NMDAR autoantibodies in some patients with herpes simplex encephalitis and suggest that autoimmunity may contribute to their symptoms. They do not establish that the listed memory, behavioral, cognitive, and psychotic symptoms—previously considered idiopathic or viral-induced—are now known to be autoimmune; the Discussion says clinical differences between antibody-positive and antibody-negative patients were not established. Page numbers are unavailable in our copy. (LLM, conf=0.87)
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Herpes simplex and varicella zoster CNS infections: clinical presentations, treatments and outcomes
Kaewpoowat, Q., Salazar, L., Aguilera, E., Wootton, S. H., & Hasbun, R. (2016) · Infection · doi:10.1007/s15010-015-0867-6 · Cited by 109 · see citing works
- Authors
- Prüss, H., Finke, C., Höltje, M., Hofmann, J., Klingbeil, C., Probst, C., Borowski, K., Ahnert‐Hilger, G., Harms, L., Schwab, J. M., Ploner, C. J., Komorowski, L., Stoecker, W., Dalmau, J., & Wandinger, K.
- Affiliations
- Charité – Universitätsmedizin Berlin (DE)
- Institució Catalana de Recerca i Estudis Avançats (ES)
- Universität Hamburg (DE)
- Corresponding author
- Prüss, Harald
- ORCID
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2012-12
- Volume
- 72
- Issue
- 6
- Pages
- 902-911
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- PMC
- PMC3725636
- OpenAlex
- W2016421065
- Cited by
- 422
- References
- 1
- Citations by year
- 2026: 22 · 2025: 24 · 2024: 18 · 2023: 22 · 2022: 30 · 2021: 26 · 2020: 31 · 2019: 27 · 2018: 28 · 2017: 39 · 2016: 39 · 2015: 45 · 2014: 35 · 2013: 26 · 2012: 8
- FWCI
- 22.45
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R01MH094741)
- National Cancer Institute (R01CA089054, R01CA107192)
- National Institute of Neurological Disorders and Stroke (R01NS077851)
- Topics
- Health Sciences › Medicine › Neurology › Autoimmune Neurological Disorders and Treatments
- Health Sciences › Medicine › Epidemiology › Herpesvirus Infections and Treatments
- Health Sciences › Medicine › Neurology › Peripheral Neuropathies and Disorders
- Keywords
- herpes simplex encephalitis, NMDA receptor antibodies, autoimmune encephalitis, IgA autoantibodies, IgG autoantibodies, IgM autoantibodies, hippocampal neurons, immunotherapy
- MeSH terms
- Adolescent, Adult, Aged, Animals, Antibodies, Cells, Cultured, Child, Embryo, Mammalian, Female, Hippocampus, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neurons, Transfection, Receptors, N-Methyl-D-Aspartate, Synapsins, Encephalitis, Herpes Simplex, Mice, Young Adult
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