ArticleProceedings of the National Academy of Sciences of the United States of America2024
Ultrahigh frequencies of peripherally matured LGI1- and CASPR2-reactive B cells characterize the cerebrospinal fluid in autoimmune encephalitis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 35 citations in OpenAlex.
- Antibody-Dependent Cellular Phagocytosis and Cytotoxicity in Patients With LGI1 and CASPR2 Encephalitis.Neurology(R) neuroimmunology & neuroinflammation · 2026Article
- Effectiveness and safety of efgartigimod in patients with anti-NMDAR or anti-LGI1 encephalitis and itsNeuroprotection (Chichester, England) · 2026Article
- The cascade to pathogenicity in autoantibody-mediated CNS diseases.Brain : a journal of neurology · 2026Review
- Kappa Free Light Chain for Diagnosis and Neurofilament Light Chain for Prognosis in Autoimmune Encephalitis.Neurology(R) neuroimmunology & neuroinflammation · 2026Observational
- Immune context and treatment timing associated with seizure freedom after rituximab in autoimmune limbic encephalitis.iScience · 2026Article
- Screening 1021 Swedish memory clinic visitors for autoantibody-mediated encephalitis.Journal of neurology · 2026Article
- CSF-Compartmentalized Antibody Glycoprofiles in NMDAR Encephalitis Associate with Etiology and Functional Recovery.Annals of neurology · 2026Article
- Plasma proteome in LGI-1 autoimmune encephalitis.Journal of neuroinflammation · 2026Article
- Immunopathological mechanisms in autoimmune encephalitis: from pathogenesis to targeted therapies.Frontiers in immunology · 2026Review
- Gut microbiota-neuroimmune crosstalk in autoimmune encephalitis: mechanistic insights and therapeutic prospects.Frontiers in microbiology · 2026Review
- Cytokine, Chemokine, and Neurofilament Light Chain Signatures in LGI1 Autoimmune Encephalitis.Annals of clinical and translational neurology · 2025Article
- Autoimmune encephalitis.Nature reviews. Disease primers · 2025Review
- Activated αβ T and reduced mucosa-associated invariant T cells in LGI1- and CASPR2-encephalitis.Brain : a journal of neurology · 2025Article
- The Clinical Trial Landscape in Autoimmune Encephalitis: Challenges and Opportunities.Neurology · 2025Review
- Permissive central tolerance plus defective peripheral checkpoints license pathogenic memory B cells in CASPR2-antibody encephalitis.Science advances · 2025Article
- Novel Meningoencephalomyelitis Associated With Vimentin IgG Autoantibodies.JAMA neurology · 2025Article
- Toward curing neurological autoimmune disorders: Biomarkers, immunological mechanisms, and therapeutic targets.Neuron · 2025Review
- Plasma cells in and around the central nervous system.Frontiers in immunology · 2025Review
- Single-cell transcriptomics for immune profiling of cerebrospinal fluid in neurological diseases.Frontiers in immunology · 2025Review
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19 authors at 5 institutions in 3 countries.
Funding
Abstract
Intrathecal synthesis of central nervous system (CNS)-reactive autoantibodies is observed across patients with autoimmune encephalitis (AE), who show multiple residual neurobehavioral deficits and relapses despite immunotherapies. We leveraged two common forms of AE, mediated by leucine-rich glioma inactivated-1 (LGI1) and contactin-associated protein-like 2 (CASPR2) antibodies, as human models to comprehensively reconstruct and profile cerebrospinal fluid (CSF) B cell receptor (BCR) characteristics. We hypothesized that the resultant observations would both inform the observed therapeutic gap and determine the contribution of intrathecal maturation to pathogenic B cell lineages. From the CSF of three patients, 381 cognate-paired IgG BCRs were isolated by cell sorting and scRNA-seq, and 166 expressed as monoclonal antibodies (mAbs). Sixty-two percent of mAbs from singleton BCRs reacted with either LGI1 or CASPR2 and, strikingly, this rose to 100% of cells in clonal groups with ≥4 members. These autoantigen-reactivities were more concentrated within antibody-secreting cells (ASCs) versus B cells (
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Registered trials
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.