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- W3200516169 abstract "Autoantibodies targeting the GABAA receptor (GABAAR) hallmark an autoimmune encephalitis presenting with frequent seizures and psychomotor abnormalities. Their pathogenic role is still not well-defined, given the common overlap with further autoantibodies and the lack of patient-derived mAbs. Five GABAAR mAbs from cerebrospinal fluid cells bound to various epitopes involving the α1 and γ2 receptor subunits, with variable binding strength and partial competition. mAbs selectively reduced GABAergic currents in neuronal cultures without causing receptor internalization. Cerebroventricular infusion of GABAAR mAbs and Fab fragments into rodents induced a severe phenotype with seizures and increased mortality, reminiscent of encephalitis patients' symptoms. Our results demonstrate direct pathogenicity of autoantibodies on GABAARs independent of Fc-mediated effector functions and provide an animal model for GABAAR encephalitis. They further provide the scientific rationale for clinical treatments using antibody depletion and can serve as tools for the development of antibody-selective immunotherapies." @default.
- W3200516169 created "2021-09-27" @default.
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- W3200516169 date "2021-11-01" @default.
- W3200516169 modified "2023-10-17" @default.
- W3200516169 title "Encephalitis patient-derived monoclonal GABAA receptor antibodies cause epileptic seizures." @default.
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- W3200516169 doi "https://doi.org/10.1084/jem.20210012" @default.
- W3200516169 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8480667" @default.
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