Journal Article

DZNE-2025-00420

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Patient-derived monoclonal LGI1 autoantibodies elicit seizures, behavioral changes and brain MRI abnormalities in rodent models.

Upadhya, M. ; Stumpf, A. ; O'Brien-Cairney, J. ; Cordero Gomez, C.DZNE* ; Döring, J. M.DZNE* ; Hoffmann, J.Extern* ; Mueller, S. ; Fukata, Y. ; van Hoof, S.DZNE* ; Dhangar, D. ; Wilson, M. A. ; Atwal, A. ; Rosch, R. ; Woodhall, G. ; Boehm-Sturm, P. ; Fukata, M. ; Kreye, J.DZNE* ; Schmitz, D.DZNE* ; Wright, S. K. ; Kornau, H.-C.DZNE* ; Prüss, H. (Last author)DZNE*

2025
Elsevier Orlando, Fla. [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.bbi.2025.02.019

Abstract: Limbic encephalitis with leucine-rich glioma inactivated 1 (LGI1) protein autoantibodies is associated with cognitive impairment, psychiatric symptoms, and seizures, including faciobrachial dystonic seizures (FBDS). Patient-derived LGI1-autoantibodies cause isolated symptoms of memory deficits in mice and seizures in rats. Using a multimodal experimental approach, we set out to improve the validity of existing in vivo rodent models to further recapitulate the full clinical syndrome of anti-LGI1 antibody mediated disease.A monoclonal anti-LGI1 antibody (anti-LGI1 mAb) derived from a patient's CSF antibody-secreting cell was infused intracerebroventricularly (ICV) into rats and mice for one or two weeks, respectively. Cellular excitability of CA3 pyramidal neurons was determined in hippocampal slices. Structural changes in mouse brains were explored using MRI. Antibody effects on behavior and brain activity of rats were studied using video-EEG.Anti-LGI1 mAbs augmented the excitability of CA3 pyramidal neurons and elicited convulsive and non-convulsive spontaneous epileptic seizures in mice and rats. Mice displayed a hypoactive and anxious phenotype during behavioral testing. MRI revealed acutely increased hippocampal volume after ICV anti-LGI1 mAb infusion. Video-EEG recordings of juvenile rats uncovered two peaks of seizure frequency during the 7-day antibody infusion period resembling the natural progression of seizures in human anti-LGI1 encephalitis.Our data strongly corroborate and extend our understanding of the direct pathogenic and epileptogenic role of human LGI1 autoantibodies.

Keyword(s): Animal model ; Human monoclonal antibody ; LGI1 ; Limbic encephalitis ; Seizure

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Contributing Institute(s):

1. Autoimmune Encephalopathies (AG Prüß)
2. Network Dysfunction (AG Schmitz)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)
2. 351 - Brain Function (POF4-351) (POF4-351)

Appears in the scientific report 2025

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 15 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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