001     144863
005     20250718154853.0
024 7 _ |a 10.17169/REFUBIUM-6306
|2 doi
024 7 _ |a urn:nbn:de:kobv:188-fudissthesis000000105584-9
|2 URN
037 _ _ |a DZNE-2020-00288
041 _ _ |a German
100 1 _ |a Leubner, Jonas
|0 P:(DE-2719)2811472
|b 0
|e First author
|u dzne
245 _ _ |a Zellbasierte Testverfahren zur Untersuchung von NMDA-Rezeptor-Antikörpern
|f - 2017-12-08
260 _ _ |c 2017
|b Charité - Universitätsmedizin Berlin
300 _ _ |a 20 pages
336 7 _ |a Habil / Postdoctoral Thesis (Non-german Habil)
|b habil
|m habil
|0 PUB:(DE-HGF)13
|s 1752846493_2397
|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 Discovered in 2007, anti-N-Methyl-D-Aspartat receptor (NMDAR) encephalitis is one of the most commonly identified causes for encephalitis. The disease often runs a severe and rapid course showing reduced state of consciousness, epileptic seizures, autonomic dysregulation and hypopnea leading to intensive care unit treatment and even death. Clinical diagnosis is made by detection of pathogenic NMDAR antibodies from a patient’s cerebrospinal fluid (CSF) or serum. Little is known about prognosis factors for the disease severity, but would be helpful for providing early and appropriate treatment. We suppose the affinity of NMDAR antibodies might be an important predicting factor. We developed highly sensitive methods to detect low concentrations of NMDAR antibodies, which can be used to analyze antibody affinity of different patients in future. Therefore, cDNA of the NR1 subunit of the NMDA receptors was amplified by polymerase chain reaction, cloned into different vectors and purified from Escheria coli for transient and stable transfection. Immunofluorescence staining on transfected HEK-cells detected lower concentrations of human NMDAR antibodies than commercial assays and flow cytometry showed exact quantification of the antibody titer, which can be used to monitor clinical progress and evaluate therapeutic success in follow-up examinations. Further CSF was conjugated with Alexa Fluor 594 to detect human and non-human NMDA receptor antibodies without secondary antibodies. The post mortem CSF analysis of a young polar bear (Ursus maritimus) suffering epileptic seizures showed strong binding to HEK cells expressing NMDA receptors. Tissue immunohistochemistry exploration demonstrated a typical neuropil signal in hippocampus and cerebellum as in human patients with NMDAR encephalitis and histopathological examination showed an encephalitis with infiltration of plasma cells. We conclude, death was caused by NMDAR encephalitis. This is the first reported non-human case and suggests, that other mammals might suffer from this treatable disease. Autoimmune response against neuropil structures might be a basic pathomechanism across mammal species.
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 NMDA-receptor-encephalitis
|2 Other
650 _ 7 |a NMDAR antibodies
|2 Other
650 _ 7 |a 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit
|2 Other
773 _ _ |a 10.17169/REFUBIUM-6306
856 4 _ |u https://refubium.fu-berlin.de/bitstream/handle/fub188/2104/diss_j.leubner.pdf?sequence=1&isAllowed=y
856 4 _ |u https://pub.dzne.de/record/144863/files/DZNE-2020-00288_Restricted.pdf
856 4 _ |u https://pub.dzne.de/record/144863/files/DZNE-2020-00288_Restricted.pdf?subformat=pdfa
|x pdfa
909 C O |p VDB
|o oai:pub.dzne.de:144863
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 0
|6 P:(DE-2719)2811472
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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