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| Home > Publications Database > Repertoireanalyse monoklonaler Antikörper des Liquors von Patienten mit anti-NMDA-Rezeptor-Enzephalitis > print |
| 001 | 144861 | ||
| 005 | 20250718155157.0 | ||
| 024 | 7 | _ | |a 10.17169/REFUBIUM-10947 |2 doi |
| 024 | 7 | _ | |a urn:nbn:de:kobv:188-fudissthesis000000105850-6 |2 URN |
| 037 | _ | _ | |a DZNE-2020-00286 |
| 041 | _ | _ | |a German |
| 100 | 1 | _ | |a Kreye, Jakob |0 P:(DE-2719)2811468 |b 0 |e First author |u dzne |
| 245 | _ | _ | |a Repertoireanalyse monoklonaler Antikörper des Liquors von Patienten mit anti-NMDA-Rezeptor-Enzephalitis |f - 2017-12-08 |
| 260 | _ | _ | |c 2017 |b Charité - Universitätsmedizin Berlin |
| 300 | _ | _ | |a 28 |
| 336 | 7 | _ | |a Habil / Postdoctoral Thesis (Non-german Habil) |b habil |m habil |0 PUB:(DE-HGF)13 |s 1752846676_2395 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a PHDTHESIS |2 BibTeX |
| 336 | 7 | _ | |a Thesis |0 2 |2 EndNote |
| 336 | 7 | _ | |a Output Types/Book |2 DataCite |
| 336 | 7 | _ | |a BOOK |2 ORCID |
| 336 | 7 | _ | |a doctoralThesis |2 DRIVER |
| 502 | _ | _ | |a Habilitationsschrift, Charité Universitätsmedizin Berlin, 2017 |c Charité Universitätsmedizin Berlin |b Habilitationsschrift |d 2017 |
| 520 | _ | _ | |a The anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most common form of autoimmune mediated brain inflammation. Typically patients initially develop psychotic changes such as substantive thought disorders and hallucinations, followed by neurological symptoms like impaired consciousness, dyskinesia, seizures, autonomic dysregulations and central hypoventilation. The detection of antibodies against the NR1 subunit of the NMDAR in the cerebrospinal fluid (CSF) is the most important diagnostic criterion. Previous works with extracted whole immunoglobulins from patients‘ CSF and serum have shown synaptic dysfunction in vitro and in vivo. Thereby an influence of further possible autoantibodies could not be eliminated and the proof of pathogenicity of NR1-specific antibodies was pending. Therefore we generated monoclonal recombinant human antibodies from CSF samples from eight patients with NMDAR encephalitis. We isolated single memory B cells and plasma cells via flow cytometry. The variable gene regions coding the heavy and light immunoglobulin chains were amplified by polymerase chain reaction. These were cloned into vectors, containing the constant gene sequence of human antibodies. We co-transfected human embryonic kidney (HEK) cells with the respective pair of heavy and light immunoglobulin chains and harvested monoclonal antibodies from the culture medium. Six percent of the generated monoclonal recombinant human antibodies showed reactivity to NR1-transfected HEK cells, likewise the typical NR1-specific staining pattern on hippocampal neurons and mouse brain sections. All NR1-specific antibodies were from the IgG isotype and have been isolated from plasma cells as well as memory B cells. Last-mentioned ones might be clinically relevant as possible origin of future relapses. Several of the NR1-specific antibodies showed clonal expansion with 100 percent identical clones and few somatic hypermutations, indicating a recent peripheral immune reaction. Furthermore we found three completely unmutated NR1-specific antibodies („naturally occurring antibodies“), suggesting incomplete immune tolerance against NR1 in these patients. Incubating hippocampal neurons with monoclonal NR1-specific antibodies caused a reduction of the NMDAR density and NMDAR-specific currents. After intravenous injections into mice, antibody enrichment in the hippocampus and cerebellum was detected. More than 95 percent of the non- NR1-binding antibodies showed specific reactivity on mouse brain sections, amongst others to neuronal surfaces, glia cells and endothelium. With these data we proved that monoclonal NR1-specific antibodies alone are neurotoxic. Therewith, any detection of these autoantibodies needs to be considered as a risk factor for neuro-psychiatric symptoms. Future work will clarify whether the presence of different NR1-specific antibodies is of prognostic relevance and whether further autoantibodies contribute to the pathophysiology. |
| 536 | _ | _ | |a 342 - Disease Mechanisms and Model Systems (POF3-342) |0 G:(DE-HGF)POF3-342 |c POF3-342 |f POF III |x 0 |
| 588 | _ | _ | |a Dataset connected to DataCite |
| 650 | _ | 7 | |a anti-NMDA-receptor-Encephalitis |2 Other |
| 650 | _ | 7 | |a monoclonal antibodies |2 Other |
| 650 | _ | 7 | |a autoantibodies |2 Other |
| 650 | _ | 7 | |a cerebrospinal fluid |2 Other |
| 650 | _ | 7 | |a electrophysiology |2 Other |
| 650 | _ | 7 | |a 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit |2 Other |
| 773 | _ | _ | |a 10.17169/REFUBIUM-10947 |
| 856 | 4 | _ | |u https://pub.dzne.de/record/144861/files/DZNE-2020-00286_Restricted.pdf |
| 856 | 4 | _ | |u https://pub.dzne.de/record/144861/files/DZNE-2020-00286_Restricted.pdf?subformat=pdfa |x pdfa |
| 909 | C | O | |p VDB |o oai:pub.dzne.de:144861 |
| 910 | 1 | _ | |a Deutsches Zentrum für Neurodegenerative Erkrankungen |0 I:(DE-588)1065079516 |k DZNE |b 0 |6 P:(DE-2719)2811468 |
| 913 | 1 | _ | |a DE-HGF |b Gesundheit |l Erkrankungen des Nervensystems |1 G:(DE-HGF)POF3-340 |0 G:(DE-HGF)POF3-342 |3 G:(DE-HGF)POF3 |2 G:(DE-HGF)POF3-300 |4 G:(DE-HGF)POF |v Disease Mechanisms and Model Systems |x 0 |
| 914 | 1 | _ | |y 2017 |
| 920 | _ | _ | |l yes |
| 920 | 1 | _ | |0 I:(DE-2719)1810003 |k AG Prüß |l Autoimmune Encephalopathies |x 0 |
| 980 | _ | _ | |a habil |
| 980 | _ | _ | |a VDB |
| 980 | _ | _ | |a I:(DE-2719)1810003 |
| 980 | _ | _ | |a UNRESTRICTED |
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