Cross-reactivity of a pathogenic autoantibody to a tumor antigen in GABA A receptor encephalitis
Year: 2021
Type: article
Abstract: Significance Antibodies recognizing the neuronal gamma-aminobutyric acid A receptor (GABA A -R) cause severe encephalitis by triggering internalization of the antibody–receptor complexes in inhibitory synapses, which leads to hyperexcitability and dysfunction of neuronal networks. From the cerebrospinal fluid of a patient with GABA A -R encephalitis we cloned a highly expressed antibody and showed that it binds the GABA A -R and influences signal transduction in neurons, explaining clinical symptoms. Using several experimental techniques, we confirmed that the antibody cross-reacts to an oncoprotein which is known to be involved in several malignancies. We showed that cross-reactivity to this oncoprotein may also be detected in two other GABA A -R patients, suggesting that such cross-reactivity is presumably a key event in the pathogenesis of GABA A -R encephalitis.
Authors: Simone M. Brändle, Manuela Cerina, Susanne Weber, Kathrin Held, Amélie F. Menke, Carmen Alcalá, David Gebert, Alexander M. Herrmann, Hannah Pellkofer, Lisa Ann Gerdes, Stefan Bittner, Frank Leypoldt, Bianca Teegen, Lars Komorowski, Tania Kümpfel, Reinhard Hohlfeld, Sven G. Meuth, Bonaventura Casanova, Nico Melzer, Eduardo Beltrán, Klaus Dornmair
Institutions: Institut für Klinische Neuroimmunologie, Ludwig-Maximilians-Universität München, University of Münster, LMU Klinikum, German Center for Infection Research, Hospital Universitari i Politècnic La Fe, Johannes Gutenberg University Mainz, Christian-Albrechts-Universität zu Kiel, Euroimmun Medizinische Labordiagnostika (Germany), Munich Cluster for Systems Neurology, Heinrich Heine University Düsseldorf
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funder: Wilhelm Sander-Stiftung
Award: G4374395499
OpenAlex ID: W3132857428