Séminaire – Harald Prüss

Lieu : Centre Broca Nouvelle-Aquitaine

Brain-targeting antibodies: new concepts from autoimmune encephalitis to psychosis to dementia

Harald Prüss, MD
– German Center for Neurodegenerative Diseases (DZNE), Berlin
– Department of Neurology and Experimental Neurology, Charité – Universitätsmedizin Berlin, Germany

https://www.dzne.de/en/research/research-areas/fundamental-research/research-groups/pruess/research-areasfocus/

Invité par Laurent Groc, IINS

Autoimmune mechanisms causing dysfunction of the brain are increasingly recognised and brought about a paradigm shift in neurology and psychiatry. Identification of numerous pathogenic auto-antibodies against neuronal tissue resulted in unprecedented diagnostic and therapeutic opportunities. Current clinical and experimental data show that diverse neuropsychiatric abnormalities may be the sole symptoms of brain autoimmunity. Affected patients are at risk that such treatable etiologies are overlooked as rheumatic or psychiatric disorders. In some patients the diagnosis can be made by detection of specific auto-antibodies directed against neuronal or glial surface proteins. These epitopes include voltage-gated potassium channels or glutamate receptors, but also novel antigens not yet tested for autoimmunity, such as cell adhesion molecules or enzymes. The identification and recombinant production of disease-defining human monoclonal autoantibodies from these patients now allow detailed analyses of the pathogenic effects, of signaling cascades leading to neuropsychiatric symptoms and potential triggers of autoimmunity. It has become clear that the perpetual discovery of novel antibodies will continue and ultimately result in a better understanding of pathological mechanisms and therapies in patients with impairment of memory, cognition, affect and mood.

10 selected Publications

1. Kornau HC, Kreye J, Stumpf A, Fukata Y, Parthier D, Sammons RP, Imbrosci B, Kurpjuweit S, Kowski AB, Fukata M, Prüss H**, Schmitz D**. 2020 Human Cerebrospinal Fluid Monoclonal LGI1 Autoantibodies Increase Neuronal Excitability. Ann Neurol. 2020 [Epub ahead of print]
2. Jurek B, Chayka M, Kreye J, Lang K, Kraus L, Fidzinski P, Kornau HC, Dao LM, Wenke NK, Long M, Rivalan M, Winter Y, Leubner J, Herken J, Mayer S, Mueller S, Boehm-Sturm P, Dirnagl U, Schmitz D, Kölch M, Prüss H. 2019 Human gestational N-methyl-d-aspartate receptor autoantibodies impair neonatal murine brain function. Ann Neurol 86(5):656-670
3. Wenke NK, Kreye J, Andrzejak E, van Casteren A, Leubner J, Murgueitio MS, Reincke SM, Secker C, Schmidl L, Geis C, Ackermann F, Nikolaus M, Garner CC, Wardemann H, Wolber G, Prüss H. 2019 N-methyl-D-aspartate receptor dysfunction by unmutated human antibodies against the NR1 subunit. Ann Neurol 85(5):771-776
4. Prüss H, Tedeschi A, Thiriot A, Lynch L, Loughhead SM, Stutte S, Mazo IB, Kopp MA, Brommer B, Blex C, Geurtz LC, Liebscher T, Niedeggen A, Dirnagl U, Bradke F, Volz MS, DeVivo MJ, Chen Y, von Andrian UH, Schwab JM (2017). Spinal cord injury-induced immunodeficiency is mediated by a sympathetic-neuroendocrine adrenal reflex. Nat Neurosci 20(11):1549-1559
5. Kreye J, Wenke NK, Chayka M, Leubner J, Murugan R, Maier N, Jurek B, Ly LT, Brandl D, Rost BR, Stumpf A, Schulz P, Radbruch H, Hauser AE, Pache F, Meisel A, Harms L, Paul F, Dirnagl U, Garner C, Schmitz D, Wardemann H, Prüss H. 2016 Human cerebrospinal fluid monoclonal N-methyl-D-aspartate receptor autoantibodies are sufficient for encephalitis pathogenesis. Brain 139:2641-52
6. Finke C, Kopp UA, Pajkert A, Behrens JR, Leypoldt F, Wuerfel JT, Ploner CJ, Prüss H*, Paul F*. 2015 Structural hippocampal damage following anti-N-methyl-D-aspartate receptor encephalitis. Biol Psychiatry 79(9):727-34
7. Prüss H, Leubner J, Wenke NK, Czirják GÁ, Szentiks CA, Greenwood AD. 2015 Anti-NMDA Receptor Encephalitis in the Polar Bear (Ursus maritimus) Knut. Sci Rep 5:12805
8. Prüss H, Finke C, Holtje M, Hofmann J, Klingbeil C, Probst C, Borowski K, Ahnert-Hilger G, Harms L, Schwab JM, Ploner CJ, Komorowski L, Stoecker W, Dalmau J, Wandinger KP. 2012 N-methyl-D-aspartate receptor antibodies in herpes simplex encephalitis. Ann Neurol 72(6):902-11
9. Prüss H, Hoeltje M, Maier N, Gomez A, Buchert R, Harms L, Ahnert-Hilger G, Schmitz D, Terborg C, Kopp U, Klingbeil C, Probst C, Kohler S, Schwab JM, Stoecker W, Dalmau J, Wandinger KP. 2012 IgA NMDA receptor antibodies are markers of synaptic immunity in slow cognitive impairment. Neurology 78(22):1743-53
10. Prüss H, Dalmau J, Harms L, Höltje M, Ahnert-Hilger G, Borowski K, Stoecker W, Wandinger KP. 2010 Retrospective analysis of NMDA receptor antibodies in encephalitis of unknown origin. Neurology 75(19):1735-9

Avec le soutien de Bordeaux Neurocampus