ArticleFrontiers in behavioral neuroscience2015
Disease-specific monoclonal antibodies targeting glutamate decarboxylase impair GABAergic neurotransmission and affect motor learning and behavioral functions.
Article in Frontiers in behavioral neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
40 citing papers in PubMed, 83 citations in OpenAlex.
- A double-blind, placebo-controlled study of rituximab in patients with stiff person syndrome.Annals of neurology · 2017Trial
- Clinical Spectrum and Outcomes of SOX1 Antibody-Associated Paraneoplastic Neurological Syndromes: A Chinese Cohort Study.Annals of clinical and translational neurology · 2026Article
- Case Report: Recurrent anti-glutamic acid decarboxylase 65 antibody-associated encephalitis in a child.Frontiers in immunology · 2026Article
- Article
- Glutamic Acid Decarboxylase 65 Antibody-associated Epilepsy and Diplopia: Two Case Reports with Literature Review.Cerebellum (London, England) · 2024Review
- Stiff-person syndrome and related disorders - diagnosis, mechanisms and therapies.Nature reviews. Neurology · 2024Review
- A candidate projective neuron type of the cerebellar cortex: the synarmotic neuron.European journal of histochemistry : EJH · 2024Review
- Consensus Paper: Latent Autoimmune Cerebellar Ataxia (LACA).Cerebellum (London, England) · 2024Article
- Overview of Paraneoplastic Autoantibody-Mediated Cognitive Impairment and Behavioral Changes: A Narrative Review.Cureus · 2024Review
- Review
- Cenobamate and Clobazam Combination as Personalized Medicine in Autoimmune-Associated Epilepsy With Anti-Gad65 Antibodies.Neurology(R) neuroimmunology & neuroinflammation · 2023Article
- Stiff Person Spectrum Disorders-An Update and Outlook on Clinical, Pathophysiological and Treatment Perspectives.Biomedicines · 2023Review
- Affinity purification of serum-derived anti-IA-2 autoantibodies in type 1 diabetes using a novel MBP-IA-2 fusion protein.Biochemistry and biophysics reports · 2023Article
- Advances in the Pathogenesis of Auto-antibody-Induced Cerebellar Synaptopathies.Cerebellum (London, England) · 2023Review
- An update on malignant tumor-related stiff person syndrome spectrum disorders: clinical mechanism, treatment, and outcomes.Frontiers in neurology · 2023Review
- Autoimmune Encephalitis: A Physician's Guide to the Clinical Spectrum Diagnosis and Management.Brain sciences · 2022Review
- Autoantibodies directed against glutamate decarboxylase interfere with glucose-stimulated insulin secretion in dispersed rat islets.International journal of experimental pathology · 2022Article
- Stiff-person Syndrome and GAD Antibody-spectrum Disorders: GABAergic Neuronal Excitability, Immunopathogenesis and Update on Antibody Therapies.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Review
- A Breakdown of Immune Tolerance in the Cerebellum.Brain sciences · 2022Review
- Serum glutamate decarboxylase antibodies and neurological disorders: when to suspect their association?Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2022Observational
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 4 countries.
Funding
Abstract
Autoantibodies to the smaller isoform of glutamate decarboxylase (GAD) can be found in patients with type 1 diabetes and a number of neurological disorders, including stiff-person syndrome, cerebellar ataxia and limbic encephalitis. The detection of disease-specific autoantibody epitopes led to the hypothesis that distinct GAD autoantibodies may elicit specific neurological phenotypes. We explored the in vitro/in vivo effects of well-characterized monoclonal GAD antibodies. We found that GAD autoantibodies present in patients with stiff person syndrome (n = 7) and cerebellar ataxia (n = 15) recognized an epitope distinct from that recognized by GAD autoantibodies present in patients with type 1 diabetes mellitus (n = 10) or limbic encephalitis (n = 4). We demonstrated that the administration of a monoclonal GAD antibody representing this epitope specificity; (1) disrupted in vitro the association of GAD with γ-Aminobutyric acid containing synaptic vesicles; (2) depressed the inhibitory synaptic transmission in cerebellar slices with a gradual time course and a lasting suppressive effect; (3) significantly decreased conditioned eyelid responses evoked in mice, with no modification of learning curves in the classical eyeblink-conditioning task; (4) markedly impaired the facilitatory effect exerted by the premotor cortex over the motor cortex in a paired-pulse stimulation paradigm; and (5) induced decreased exploratory behavior and impaired locomotor function in rats. These findings support the specific targeting of GAD by its autoantibodies in the pathogenesis of stiff-person syndrome and cerebellar ataxia. Therapies of these disorders based on selective removal of such GAD antibodies could be envisioned.
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