ArticleNeurology(R) neuroimmunology & neuroinflammation2023
Antibodies Against Glutamic Acid Decarboxylase 65 Are Locally Produced in the CSF and Arise During Affinity Maturation.
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Article in Neurology(R) neuroimmunology & neuroinflammation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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9 citing papers in PubMed, 15 citations in OpenAlex.
- Immune cell profiling reveals expanded stem cell-like memory T cells in anti-GAD65-associated neurological syndromes.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Diagnostic challenge of GAD65-associated autoimmune encephalitis mimicking post-traumatic complications in an older adult: a case report.Frontiers in medicine · 2026Article
- Successful fresh formulation CD19 CAR-T cell therapy for GAD65 antibody-mediated cerebellar ataxia. A Case Report.Frontiers in immunology · 2026Article
- Clinical Features and Outcomes of Glutamic Acid Decarboxylase-65 Antibody-Associated Pure Cerebellar Ataxia and Stiff Person Syndrome Spectrum Disorders: A Single-Center Cohort Study.European journal of neurology · 2025Observational
- Ten Years ofNeurology(R) neuroimmunology & neuroinflammation · 2025Article
- Glutamic Acid Decarboxylase 65 Antibody-associated Epilepsy and Diplopia: Two Case Reports with Literature Review.Cerebellum (London, England) · 2024Review
- Early Neuroaxonal Damage in Neurologic Disorders Associated With GAD65 Antibodies.Neurology(R) neuroimmunology & neuroinflammation · 2024Article
- Review
- Stiff Person Spectrum Disorders-An Update and Outlook on Clinical, Pathophysiological and Treatment Perspectives.Biomedicines · 2023Review
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Authors and funding
14 authors at 1 institution in 3 countries.
Michelle BiljeckiFrom the Institute of Clinical Neuroimmunology (M.B., K.E., E.B., S.W., S.M., A.T., A.F.-H., T.K., M.K., E.M., F.S.T.), University Hospital, Ludwig-Maximilians-Universität Munich; Biomedical Center (BMC) (M.B., K.E., E.B., S.W., S.M., A.T., A.F.-H., T.K., M.K., E.M., F.S.T.), Medical Faculty, Ludwig-Maximilians-Universität Munich, Martinsried; Graduate School of Systemic Neurosciences Ludwig-Maximilians-Universität Munich (M.B., K.E.); Munich Cluster for Systems Neurology (SyNergy) (E.B., M.K., F.S.T.); Innate Immunity Unit (A.T.), Institut Pasteur, Inserm U1223, Paris, France; Université de Paris (A.T.), Sorbonne Paris Cité, France; Institute of Laboratory Medicine (P.E.), University Hospital, LMU Munich; Institute of Clinical and Molecular Virology (P.S.), University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg; and Department of Neurology (J.L.), University Hospital Ulm, Germany.
Katharina EisenhutFrom the Institute of Clinical Neuroimmunology (M.B., K.E., E.B., S.W., S.M., A.T., A.F.-H., T.K., M.K., E.M., F.S.T.), University Hospital, Ludwig-Maximilians-Universität Munich; Biomedical Center (BMC) (M.B., K.E., E.B., S.W., S.M., A.T., A.F.-H., T.K., M.K., E.M., F.S.T.), Medical Faculty, Ludwig-Maximilians-Universität Munich, Martinsried; Graduate School of Systemic Neurosciences Ludwig-Maximilians-Universität Munich (M.B., K.E.); Munich Cluster for Systems Neurology (SyNergy) (E.B., M.K., F.S.T.); Innate Immunity Unit (A.T.), Institut Pasteur, Inserm U1223, Paris, France; Université de Paris (A.T.), Sorbonne Paris Cité, France; Institute of Laboratory Medicine (P.E.), University Hospital, LMU Munich; Institute of Clinical and Molecular Virology (P.S.), University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg; and Department of Neurology (J.L.), University Hospital Ulm, Germany.ORCID 0000-0001-6448-3126
Eduardo BeltránFrom the Institute of Clinical Neuroimmunology (M.B., K.E., E.B., S.W., S.M., A.T., A.F.-H., T.K., M.K., E.M., F.S.T.), University Hospital, Ludwig-Maximilians-Universität Munich; Biomedical Center (BMC) (M.B., K.E., E.B., S.W., S.M., A.T., A.F.-H., T.K., M.K., E.M., F.S.T.), Medical Faculty, Ludwig-Maximilians-Universität Munich, Martinsried; Graduate School of Systemic Neurosciences Ludwig-Maximilians-Universität Munich (M.B., K.E.); Munich Cluster for Systems Neurology (SyNergy) (E.B., M.K., F.S.T.); Innate Immunity Unit (A.T.), Institut Pasteur, Inserm U1223, Paris, France; Université de Paris (A.T.), Sorbonne Paris Cité, France; Institute of Laboratory Medicine (P.E.), University Hospital, LMU Munich; Institute of Clinical and Molecular Virology (P.S.), University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg; and Department of Neurology (J.L.), University Hospital Ulm, Germany.
Stephan WinklmeierFrom the Institute of Clinical Neuroimmunology (M.B., K.E., E.B., S.W., S.M., A.T., A.F.-H., T.K., M.K., E.M., F.S.T.), University Hospital, Ludwig-Maximilians-Universität Munich; Biomedical Center (BMC) (M.B., K.E., E.B., S.W., S.M., A.T., A.F.-H., T.K., M.K., E.M., F.S.T.), Medical Faculty, Ludwig-Maximilians-Universität Munich, Martinsried; Graduate School of Systemic Neurosciences Ludwig-Maximilians-Universität Munich (M.B., K.E.); Munich Cluster for Systems Neurology (SyNergy) (E.B., M.K., F.S.T.); Innate Immunity Unit (A.T.), Institut Pasteur, Inserm U1223, Paris, France; Université de Paris (A.T.), Sorbonne Paris Cité, France; Institute of Laboratory Medicine (P.E.), University Hospital, LMU Munich; Institute of Clinical and Molecular Virology (P.S.), University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg; and Department of Neurology (J.L.), University Hospital Ulm, Germany.ORCID 0000-0001-8675-0387
Simone MaderFrom the Institute of Clinical Neuroimmunology (M.B., K.E., E.B., S.W., S.M., A.T., A.F.-H., T.K., M.K., E.M., F.S.T.), University Hospital, Ludwig-Maximilians-Universität Munich; Biomedical Center (BMC) (M.B., K.E., E.B., S.W., S.M., A.T., A.F.-H., T.K., M.K., E.M., F.S.T.), Medical Faculty, Ludwig-Maximilians-Universität Munich, Martinsried; Graduate School of Systemic Neurosciences Ludwig-Maximilians-Universität Munich (M.B., K.E.); Munich Cluster for Systems Neurology (SyNergy) (E.B., M.K., F.S.T.); Innate Immunity Unit (A.T.), Institut Pasteur, Inserm U1223, Paris, France; Université de Paris (A.T.), Sorbonne Paris Cité, France; Institute of Laboratory Medicine (P.E.), University Hospital, LMU Munich; Institute of Clinical and Molecular Virology (P.S.), University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg; and Department of Neurology (J.L.), University Hospital Ulm, Germany.
Anna ThallerFrom the Institute of Clinical Neuroimmunology (M.B., K.E., E.B., S.W., S.M., A.T., A.F.-H., T.K., M.K., E.M., F.S.T.), University Hospital, Ludwig-Maximilians-Universität Munich; Biomedical Center (BMC) (M.B., K.E., E.B., S.W., S.M., A.T., A.F.-H., T.K., M.K., E.M., F.S.T.), Medical Faculty, Ludwig-Maximilians-Universität Munich, Martinsried; Graduate School of Systemic Neurosciences Ludwig-Maximilians-Universität Munich (M.B., K.E.); Munich Cluster for Systems Neurology (SyNergy) (E.B., M.K., F.S.T.); Innate Immunity Unit (A.T.), Institut Pasteur, Inserm U1223, Paris, France; Université de Paris (A.T.), Sorbonne Paris Cité, France; Institute of Laboratory Medicine (P.E.), University Hospital, LMU Munich; Institute of Clinical and Molecular Virology (P.S.), University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg; and Department of Neurology (J.L.), University Hospital Ulm, Germany.
Peter EichhornFrom the Institute of Clinical Neuroimmunology (M.B., K.E., E.B., S.W., S.M., A.T., A.F.-H., T.K., M.K., E.M., F.S.T.), University Hospital, Ludwig-Maximilians-Universität Munich; Biomedical Center (BMC) (M.B., K.E., E.B., S.W., S.M., A.T., A.F.-H., T.K., M.K., E.M., F.S.T.), Medical Faculty, Ludwig-Maximilians-Universität Munich, Martinsried; Graduate School of Systemic Neurosciences Ludwig-Maximilians-Universität Munich (M.B., K.E.); Munich Cluster for Systems Neurology (SyNergy) (E.B., M.K., F.S.T.); Innate Immunity Unit (A.T.), Institut Pasteur, Inserm U1223, Paris, France; Université de Paris (A.T.), Sorbonne Paris Cité, France; Institute of Laboratory Medicine (P.E.), University Hospital, LMU Munich; Institute of Clinical and Molecular Virology (P.S.), University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg; and Department of Neurology (J.L.), University Hospital Ulm, Germany.
Philipp SteiningerFrom the Institute of Clinical Neuroimmunology (M.B., K.E., E.B., S.W., S.M., A.T., A.F.-H., T.K., M.K., E.M., F.S.T.), University Hospital, Ludwig-Maximilians-Universität Munich; Biomedical Center (BMC) (M.B., K.E., E.B., S.W., S.M., A.T., A.F.-H., T.K., M.K., E.M., F.S.T.), Medical Faculty, Ludwig-Maximilians-Universität Munich, Martinsried; Graduate School of Systemic Neurosciences Ludwig-Maximilians-Universität Munich (M.B., K.E.); Munich Cluster for Systems Neurology (SyNergy) (E.B., M.K., F.S.T.); Innate Immunity Unit (A.T.), Institut Pasteur, Inserm U1223, Paris, France; Université de Paris (A.T.), Sorbonne Paris Cité, France; Institute of Laboratory Medicine (P.E.), University Hospital, LMU Munich; Institute of Clinical and Molecular Virology (P.S.), University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg; and Department of Neurology (J.L.), University Hospital Ulm, Germany.
Andrea Flierl-HechtFrom the Institute of Clinical Neuroimmunology (M.B., K.E., E.B., S.W., S.M., A.T., A.F.-H., T.K., M.K., E.M., F.S.T.), University Hospital, Ludwig-Maximilians-Universität Munich; Biomedical Center (BMC) (M.B., K.E., E.B., S.W., S.M., A.T., A.F.-H., T.K., M.K., E.M., F.S.T.), Medical Faculty, Ludwig-Maximilians-Universität Munich, Martinsried; Graduate School of Systemic Neurosciences Ludwig-Maximilians-Universität Munich (M.B., K.E.); Munich Cluster for Systems Neurology (SyNergy) (E.B., M.K., F.S.T.); Innate Immunity Unit (A.T.), Institut Pasteur, Inserm U1223, Paris, France; Université de Paris (A.T.), Sorbonne Paris Cité, France; Institute of Laboratory Medicine (P.E.), University Hospital, LMU Munich; Institute of Clinical and Molecular Virology (P.S.), University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg; and Department of Neurology (J.L.), University Hospital Ulm, Germany.
Jan LewerenzFrom the Institute of Clinical Neuroimmunology (M.B., K.E., E.B., S.W., S.M., A.T., A.F.-H., T.K., M.K., E.M., F.S.T.), University Hospital, Ludwig-Maximilians-Universität Munich; Biomedical Center (BMC) (M.B., K.E., E.B., S.W., S.M., A.T., A.F.-H., T.K., M.K., E.M., F.S.T.), Medical Faculty, Ludwig-Maximilians-Universität Munich, Martinsried; Graduate School of Systemic Neurosciences Ludwig-Maximilians-Universität Munich (M.B., K.E.); Munich Cluster for Systems Neurology (SyNergy) (E.B., M.K., F.S.T.); Innate Immunity Unit (A.T.), Institut Pasteur, Inserm U1223, Paris, France; Université de Paris (A.T.), Sorbonne Paris Cité, France; Institute of Laboratory Medicine (P.E.), University Hospital, LMU Munich; Institute of Clinical and Molecular Virology (P.S.), University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg; and Department of Neurology (J.L.), University Hospital Ulm, Germany.
Tania KümpfelFrom the Institute of Clinical Neuroimmunology (M.B., K.E., E.B., S.W., S.M., A.T., A.F.-H., T.K., M.K., E.M., F.S.T.), University Hospital, Ludwig-Maximilians-Universität Munich; Biomedical Center (BMC) (M.B., K.E., E.B., S.W., S.M., A.T., A.F.-H., T.K., M.K., E.M., F.S.T.), Medical Faculty, Ludwig-Maximilians-Universität Munich, Martinsried; Graduate School of Systemic Neurosciences Ludwig-Maximilians-Universität Munich (M.B., K.E.); Munich Cluster for Systems Neurology (SyNergy) (E.B., M.K., F.S.T.); Innate Immunity Unit (A.T.), Institut Pasteur, Inserm U1223, Paris, France; Université de Paris (A.T.), Sorbonne Paris Cité, France; Institute of Laboratory Medicine (P.E.), University Hospital, LMU Munich; Institute of Clinical and Molecular Virology (P.S.), University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg; and Department of Neurology (J.L.), University Hospital Ulm, Germany.
Martin KerschensteinerFrom the Institute of Clinical Neuroimmunology (M.B., K.E., E.B., S.W., S.M., A.T., A.F.-H., T.K., M.K., E.M., F.S.T.), University Hospital, Ludwig-Maximilians-Universität Munich; Biomedical Center (BMC) (M.B., K.E., E.B., S.W., S.M., A.T., A.F.-H., T.K., M.K., E.M., F.S.T.), Medical Faculty, Ludwig-Maximilians-Universität Munich, Martinsried; Graduate School of Systemic Neurosciences Ludwig-Maximilians-Universität Munich (M.B., K.E.); Munich Cluster for Systems Neurology (SyNergy) (E.B., M.K., F.S.T.); Innate Immunity Unit (A.T.), Institut Pasteur, Inserm U1223, Paris, France; Université de Paris (A.T.), Sorbonne Paris Cité, France; Institute of Laboratory Medicine (P.E.), University Hospital, LMU Munich; Institute of Clinical and Molecular Virology (P.S.), University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg; and Department of Neurology (J.L.), University Hospital Ulm, Germany.
Edgar MeinlFrom the Institute of Clinical Neuroimmunology (M.B., K.E., E.B., S.W., S.M., A.T., A.F.-H., T.K., M.K., E.M., F.S.T.), University Hospital, Ludwig-Maximilians-Universität Munich; Biomedical Center (BMC) (M.B., K.E., E.B., S.W., S.M., A.T., A.F.-H., T.K., M.K., E.M., F.S.T.), Medical Faculty, Ludwig-Maximilians-Universität Munich, Martinsried; Graduate School of Systemic Neurosciences Ludwig-Maximilians-Universität Munich (M.B., K.E.); Munich Cluster for Systems Neurology (SyNergy) (E.B., M.K., F.S.T.); Innate Immunity Unit (A.T.), Institut Pasteur, Inserm U1223, Paris, France; Université de Paris (A.T.), Sorbonne Paris Cité, France; Institute of Laboratory Medicine (P.E.), University Hospital, LMU Munich; Institute of Clinical and Molecular Virology (P.S.), University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg; and Department of Neurology (J.L.), University Hospital Ulm, Germany.ORCID 0000-0002-2570-6785
Franziska S ThalerFrom the Institute of Clinical Neuroimmunology (M.B., K.E., E.B., S.W., S.M., A.T., A.F.-H., T.K., M.K., E.M., F.S.T.), University Hospital, Ludwig-Maximilians-Universität Munich; Biomedical Center (BMC) (M.B., K.E., E.B., S.W., S.M., A.T., A.F.-H., T.K., M.K., E.M., F.S.T.), Medical Faculty, Ludwig-Maximilians-Universität Munich, Martinsried; Graduate School of Systemic Neurosciences Ludwig-Maximilians-Universität Munich (M.B., K.E.); Munich Cluster for Systems Neurology (SyNergy) (E.B., M.K., F.S.T.); Innate Immunity Unit (A.T.), Institut Pasteur, Inserm U1223, Paris, France; Université de Paris (A.T.), Sorbonne Paris Cité, France; Institute of Laboratory Medicine (P.E.), University Hospital, LMU Munich; Institute of Clinical and Molecular Virology (P.S.), University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg; and Department of Neurology (J.L.), University Hospital Ulm, Germany. franziska.thaler@med.uni-muenchen.de.
Inserm · FR
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesAntibodies (Abs) against the cytoplasmic protein glutamic acid decarboxylase 65 (GAD65) are detected in patients with neurologic syndromes together referred to as GAD65-Ab spectrum disorders. The response of some of these patients to plasma exchange or immunoglobulins indicates that GAD65-Abs could contribute to disease pathogenesis at least at some stages of disease. However, the involvement of GAD65-reactive B cells in the CNS is incompletely understood.
methodsWe studied 7 patients with high levels of GAD65-Abs and generated monoclonal Abs (mAbs) derived from single cells in the CSF. Sequence characteristics, reactivity to GAD65, and the role of somatic hypermutations of the mAbs were analyzed.
resultsTwelve CSF-derived mAbs were generated originating from 3 patients with short disease duration, and 7/12 of these mAbs (58%) were GAD65 reactive in at least 1 detection assay. Four of 12 (33%) were definitely positive in all 3 detection assays. The intrathecal anti-GAD65 response was polyclonal. GAD65-Abs were mostly of the IgG1 subtype and had undergone affinity maturation. Reversion of 2 GAD65-reactive mAbs to their corresponding germline-encoded unmutated common ancestors abolished GAD65 reactivity. DISCUSSION: GAD65-specific B cells are present in the CNS and represent a sizable fraction of CSF B cells early in the disease course. The anti-GAD65 response in the CSF is polyclonal and shows evidence of antigen-driven affinity maturation required for GAD65 recognition. Our data support the hypothesis that the accumulation of GAD65-specific B cells and plasma cells in the CSF is an important feature of early disease stages.
Indexed as
AutoantibodiesGlutamate DecarboxylaseAntibodies, MonoclonalHumansImmunoglobulin GSyndromeAntibodies, MonoclonalAutoantibodiesGlutamate DecarboxylaseImmunoglobulin G
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