![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
Tools
Tools
Preview |
PDF (Original Article)
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
5MB |
![[thumbnail of Supplementary Data]](https://edoc.mdc-berlin.de/style/images/fileicons/other.png) |
Other (Supplementary Data)
88MB |
| Item Type: | Article |
|---|---|
| Title: | Encephalitis patient-derived monoclonal GABA(A) receptor antibodies cause epileptic seizures |
| Creators Name: | Kreye, J., Wright, S.K., van Casteren, A., Stoeffler, L., Machule, M.L., Reincke, S.M., Nikolaus, M., van Hoof, S., Sanchez-Sendin, E., Homeyer, M.A., Gómez, C.C., Kornau, H.C., Schmitz, D., Kaindl, A.M., Boehm-Sturm, P., Mueller, S., Wilson, M.A., Upadhya, M.A., Dhangar, D.R., Greenhill, S., Woodhall, G., Turko, P., Vida, I., Garner, C.C., Wickel, J., Geis, C., Fukata, Y., Fukata, M. and Prüss, H. |
| Abstract: | Autoantibodies targeting the GABA(A) receptor (GABA(A)R) 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 GABA(A)R 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 GABA(A)R 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 GABA(A)Rs independent of Fc-mediated effector functions and provide an animal model for GABA(A)R 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. |
| Keywords: | Autoantibodies, Autoantigens, Cultured Cells, Encephalitis, Epilepsy, GABA-A Receptors, HEK293 Cells, Hippocampus, Monoclonal Antibodies, Neurons, Seizures, Animals, Mice |
| Source: | Journal of Experimental Medicine |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Volume: | 218 |
| Number: | 11 |
| Page Range: | e20210012 |
| Date: | 1 November 2021 |
| Additional Information: | ©2021 Kreye et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
| Official Publication: | https://doi.org/10.1084/jem.20210012 |
| PubMed: | View item in PubMed |
Repository Staff Only: item control page
