ArticleBrain : a journal of neurology2019
Glycine receptor autoantibodies disrupt inhibitory neurotransmission.
Article in Brain : a journal of neurology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 83 citations in OpenAlex.
- Associations of viral infections and antiviral vaccinations with anti-NMDAR and other forms of autoimmune encephalitis.Brain, behavior, & immunity - health · 2026Review
- High-Affinity Human Germline and Mutated Autoantibodies Commonly Cross-React to Self-Antigens in 5 Subgroups of Autoimmune Encephalitis.Neurology(R) neuroimmunology & neuroinflammation · 2026Article
- Purpose-Adaptable Reinforced 3D Hyaluronic-Acid Based Platform to Study Pathomechanisms of the Central Nervous System.Advanced healthcare materials · 2026Article
- Cryo-EM of autoantibody-bound NMDA receptors reveals antigenic hotspots in an active immunization model of anti-NMDAR encephalitis.Science advances · 2026Article
- Polyclonal glycine receptor aAbs: a challenge for personalized epitope characterization.Frontiers in molecular neuroscience · 2026Article
- The spatial architecture of neuroimmune interactions in epilepsy.Frontiers in immunology · 2026Review
- Impacts of conditionally essential amino acids, cysteine, and tyrosine on intestinal inflammation in celiac disease.Amino acids · 2025Review
- Binding patterns of glycine receptor autoantibodies are related to clinical syndromes.Acta neuropathologica communications · 2025Article
- Autoantibody profiling using microarray identifies biomarkers associated with chemoimmunotherapy efficacy and immune-related adverse events in lung cancer patients.Clinical and experimental medicine · 2025Article
- Neurodegeneration and the immune system: lessons from autoimmune encephalitis.Journal of neurology · 2025Review
- Neurophysiological Insights into the Pathophysiology of Stiff-Person Spectrum Disorders.Movement disorders clinical practice · 2025Review
- Impaired Presynaptic Function Contributes Significantly to the Pathology of Glycine Receptor Autoantibodies.Neurology(R) neuroimmunology & neuroinflammation · 2025Article
- Histopathological Investigation of Progressive Encephalomyelitis with Rigidity and Myoclonus: An Autopsy Case Characterized by Oculomotor Dysfunction and Autonomic Failure.Internal medicine (Tokyo, Japan) · 2025Article
- Chimeric antigen receptor T-cell therapy for stiff-person syndrome: bridging innovation and clinical challenges in neuroimmunology.Therapeutic advances in neurological disorders · 2025Review
- Autologous hematopoietic stem cell transplantation in a patient with multi-refractory stiff person syndrome.Bone marrow transplantation · 2025Article
- Ten Years ofNeurology(R) neuroimmunology & neuroinflammation · 2025Article
- Structural basis for antibody-mediated NMDA receptor clustering and endocytosis in autoimmune encephalitis.Nature structural & molecular biology · 2024Article
- Fluorescence-detection size-exclusion chromatography specifically detects autoantibodies targeting the ganglionic acetylcholine receptor in patients with autoimmune autonomic ganglionopathy.Journal of neuroimmunology · 2024Article
- Progressive Encephalomyelitis With Rigidity and Myoclonus With Glycine Receptor and GAD65 Antibodies: Case Report and Potential Mechanisms.Neurology(R) neuroimmunology & neuroinflammation · 2024Article
- Stiff-person syndrome and related disorders - diagnosis, mechanisms and therapies.Nature reviews. Neurology · 2024Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Chloride-permeable glycine receptors have an important role in fast inhibitory neurotransmission in the spinal cord and brainstem. Human immunoglobulin G (IgG) autoantibodies to glycine receptors are found in a substantial proportion of patients with progressive encephalomyelitis with rigidity and myoclonus, and less frequently in other variants of stiff person syndrome. Demonstrating a pathogenic role of glycine receptor autoantibodies would help justify the use of immunomodulatory therapies and provide insight into the mechanisms involved. Here, purified IgGs from four patients with progressive encephalomyelitis with rigidity and myoclonus or stiff person syndrome, and glycine receptor autoantibodies, were observed to disrupt profoundly glycinergic neurotransmission. In whole-cell patch clamp recordings from cultured rat spinal motor neurons, glycinergic synaptic currents were almost completely abolished following incubation in patient IgGs. Most human autoantibodies targeting other CNS neurotransmitter receptors, such as N-methyl-d-aspartate (NMDA) receptors, affect whole cell currents only after several hours incubation and this effect has been shown to be the result of antibody-mediated crosslinking and internalization of receptors. By contrast, we observed substantial reductions in glycinergic currents with all four patient IgG preparations with 15 min of exposure to patient IgGs. Moreover, monovalent Fab fragments generated from the purified IgG of three of four patients also profoundly reduced glycinergic currents compared with control Fab-IgG. We conclude that human glycine receptor autoantibodies disrupt glycinergic neurotransmission, and also suggest that the pathogenic mechanisms include direct antagonistic actions on glycine receptors.
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