Autoimmune Encephalopathies
Prof. Dr. Harald Prüß
Group Leader
c/o Charité Universitätsmedizin Berlin
CharitéCrossOver
Charitéplatz 1
10117  Berlin

harald.pruess@dzne.de
 +49 30 4505-60399

Areas of investigation/research focus

An increasing number of neuropsychiatric diseases are caused by pathogenic anti-neuronal antibodies, ranging from acute encephalitis to slowly progressive dementia. Antibodies against the NMDA-type glutamate receptor are prototypical for this new disease group. Patients with IgG NMDA receptor autoantibodies develop a severe encephalitis with psychiatric features. In contrast, IgA antibodies are associated with progressive cognitive impairment.

Our research focuses on the detailed analysis of mechanisms of autoantibody-mediated impairment of neuronal function. For this, individual antibody-secreting cells from the cerebrospinal fluid of affected patients are isolated. Molecular biology techniques then allow the recombinant production of autoantibodies derived from these cells. This novel methodology could, for the first time, demonstrate that the antibodies are directly pathogenic, thus leading to synaptic changes in hippocampal neurons. We are currently expanding the technology to additional disease-related antibodies, such as against AMPA receptors, GABA receptors, glycine receptors, LGI1, GAD or IgLON5. The monoclonal human antibodies are ideal tools for high-resolution microscopy and targets for innovative immunotherapies in patients with psychosis or dementia.

Experimental results provide insight into the molecular cascades of neuronal damage, thus representing an important translational approach to identify patients that could benefit from immunotherapy.

Key Publications

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. Human gestational N-methyl-d-aspartate receptor autoantibodies impair neonatal murine brain function. Ann Neurol. 2019 Nov 01; 86:656-670. doi: 10.1002/ana.25552
Harald Prüss, Andrea Tedeschi, Aude Thiriot, Lydia Lynch, Scott M Loughhead, Susanne Stutte, Irina B Mazo, Marcel A Kopp, Benedikt Brommer, Christian Blex, Laura-Christin Geurtz, Thomas Liebscher, Andreas Niedeggen, Ulrich Dirnagl, Frank Bradke, Magdalena S Volz, Michael J DeVivo, Yuying Chen, Ulrich H Von Andrian, Jan M Schwab. Spinal cord injury-induced immunodeficiency is mediated by a sympathetic-neuroendocrine adrenal reflex. Nature Neuroscience. 2016 Dec 31; 20:1549-1559. doi: 10.1038/nn.4643
Jakob Kreye, Nina K. Wenke, Mariya Chayka, Jonas Leubner, Rajagopal Murugan, Nikolaus Maier, Betty Jurek, Lam-Thanh Ly, Doreen Brandl, Benjamin R. Rost, Alexander Stumpf, Paulina Schulz, Helena Radbruch, Anja E. Hauser, Florence Pache, Andreas Meisel, Lutz Harms, Friedemann Paul, Ulrich Dirnagl, Craig Garner, Dietmar Schmitz, Hedda Wardemann, Harald Prüss. Human cerebrospinal fluid monoclonal N-methyl-D-aspartate receptor autoantibodies are sufficient for encephalitis pathogenesis. Brain. 2016 Sep 30; 139:2641-2652. doi: 10.1093/brain/aww208
Prüss, Leubner, Wenke, Czirják, Szentiks, Greenwood. Anti-NMDA Receptor Encephalitis in the Polar Bear (Ursus maritimus) Knut. Scientific Reports. 2015 Aug 26; 5 doi: 10.1038/srep12805
Prüss H, Finke C, Höltje 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. N-methyl-D-aspartate receptor antibodies in herpes simplex encephalitis. Ann Neurol. 2012 Dec 01; 72:902-11.

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