ArticleProceedings of the National Academy of Sciences of the United States of America2006
Human lupus autoantibodies against NMDA receptors mediate cognitive impairment.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 166 papers, 1 of them a synthesis that pooled it.
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Who cites it
166 citing papers in PubMed, 1 synthesis or guideline pooled it, 414 citations in OpenAlex.
- Beyond anti-SSA and anti-SSB. The clinical significance of new antibodies in the diagnosis of Sjögren disease.Rheumatology international · 2026Pooled it
- Advances and pitfalls in anti-double-stranded DNA autoantibody detection and interpretation.World journal of biological chemistry · 2026Review
- Endothelial Dysfunction: Insights into Systemic Lupus Erythematosus-associated Cardiovascular Disease and Neuropsychiatric Manifestations.Journal of cardiovascular translational research · 2026Review
- Microbial-Immune Interplay in CNS Autoimmune Diseases: Lessons from Animal Models and Clinical Studies.European journal of immunology · 2026Review
- Cryo-EM of autoantibody-bound NMDA receptors reveals antigenic hotspots in an active immunization model of anti-NMDAR encephalitis.Science advances · 2026Article
- Distinct metabolic patterns of neuropsychiatric systemic lupus erythematosus on hierarchical cluster analysis.European journal of nuclear medicine and molecular imaging · 2025Article
- Anti-P antibodies that impair memory perturb hippocampal glutamatergic receptor trafficking, synapse structure and microglia.Molecular medicine (Cambridge, Mass.) · 2025Article
- Diffuse neuropsychiatric lupus: Clinical evidence, immune-mediated mechanisms, and therapeutic insights.Seminars in immunology · 2025Review
- Evaluation of MRI-based brain oxygen extraction fraction mapping in patients with systemic lupus erythematosus.Lupus science & medicine · 2025Article
- MRI-based neuroimaging alterations in immune-related skin diseases: a comprehensive review.Archives of dermatological research · 2025Review
- Towards precision medicine for systemic lupus erythematosus and neuropsychiatric manifestations.Expert review of precision medicine and drug development · 2025Article
- The MRL Model: A Valuable Tool in Studies of Autoimmunity-Brain Interactions.Methods in molecular biology (Clifton, N.J.) · 2025Review
- Blood-Brain Barrier Disruption in Neuroimmunological Disease.International journal of molecular sciences · 2024Review
- Assessing the COX-2/PGE2 Ratio and Anti-Nucleosome Autoantibodies as Biomarkers of Autism Spectrum Disorders: Using Combined ROC Curves to Improve Diagnostic Values.Current issues in molecular biology · 2024Article
- Lupus autoantibodies initiate neuroinflammation sustained by continuous HMGB1:RAGE signaling and reversed by increased LAIR-1 expression.Nature immunology · 2024Article
- Correlation between neurofilament, HMGB1, MMP9, ds DNA blood levels and cognitive impairment in patients with neuropsychiatric systemic lupus erythematosus.Caspian journal of internal medicine · 2024Article
- Social stress induces autoimmune responses against the brain.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Monomeric streptavidin phage display allows efficient immobilization of bacteriophages on magnetic particles for the capture, separation, and detection of bacteria.Scientific reports · 2023Article
- Neural Regeneration in Dry Eye Secondary to Systemic Lupus Erythematosus Is Also Disrupted like in Rheumatoid Arthritis, but in a Progressive Fashion.International journal of molecular sciences · 2023Article
- Preclinical characterization of the Toll-like receptor 7/8 antagonist MHV370 for lupus therapy.Cell reports. Medicine · 2023Article
106 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuropsychiatric systemic lupus erythematosus, which often entails cognitive disturbances and memory loss, has become a major complication for lupus patients. Previously, we developed a murine model of neuropsychiatric lupus based on Abs that cross-react with dsDNA and the NMDA receptor (NMDAR). We showed that these murine Abs impair cognition when they access the CNS through a breach in the blood-brain barrier (BBB) triggered by lipopolysaccharide. Because studies show that lupus patients possess anti-NMDAR Abs in their serum and cerebrospinal fluid, we decided to investigate whether these human Abs contribute to cognitive dysfunction. Here, we show that serum with reactivity to DNA and NMDAR extracted from lupus patients elicited cognitive impairment in mice receiving the serum intravenously and given lipopolysaccharide to compromise the BBB integrity. Brain histopathology showed hippocampal neuron damage, and behavioral testing revealed hippocampus-dependent memory impairment. To determine whether anti-NMDAR Abs exist in the brains of systemic lupus erythematosus patients, we eluted IgG from a patient's brain. The IgG bound DNA and NMDAR and caused neuronal apoptosis when injected into mouse brains. We examined four more brains of patients with neuropsychiatric lupus and found that they displayed endogenous IgG colocalizing with anti-NMDAR Abs. Our results indicate that lupus patients have circulating anti-NMDAR Abs capable of causing neuronal damage and memory deficit, if they breach the BBB, and that the Abs exist within patients' brains. Which aspects of neuropsychiatric lupus may be mediated by anti-NMDAR Abs, how often, and in which patients are now important clinical questions.
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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.