000144863 001__ 144863
000144863 005__ 20250718154853.0
000144863 0247_ $$2doi$$a10.17169/REFUBIUM-6306
000144863 0247_ $$2URN$$aurn:nbn:de:kobv:188-fudissthesis000000105584-9
000144863 037__ $$aDZNE-2020-00288
000144863 041__ $$aGerman
000144863 1001_ $$0P:(DE-2719)2811472$$aLeubner, Jonas$$b0$$eFirst author$$udzne
000144863 245__ $$aZellbasierte Testverfahren zur Untersuchung von NMDA-Rezeptor-Antikörpern$$f - 2017-12-08
000144863 260__ $$bCharité - Universitätsmedizin Berlin$$c2017
000144863 300__ $$a20 pages
000144863 3367_ $$0PUB:(DE-HGF)13$$2PUB:(DE-HGF)$$aHabil / Postdoctoral Thesis (Non-german Habil)$$bhabil$$mhabil$$s1752846493_2397
000144863 3367_ $$2BibTeX$$aPHDTHESIS
000144863 3367_ $$02$$2EndNote$$aThesis
000144863 3367_ $$2DataCite$$aOutput Types/Book
000144863 3367_ $$2ORCID$$aBOOK
000144863 3367_ $$2DRIVER$$adoctoralThesis
000144863 502__ $$aHabilitationsschrift, Charité Universitätsmedizin Berlin, 2017$$bHabilitationsschrift$$cCharité Universitätsmedizin Berlin$$d2017
000144863 520__ $$aDiscovered 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.
000144863 536__ $$0G:(DE-HGF)POF3-342$$a342 - Disease Mechanisms and Model Systems (POF3-342)$$cPOF3-342$$fPOF III$$x0
000144863 588__ $$aDataset connected to DataCite
000144863 650_7 $$2Other$$aNMDA-receptor-encephalitis
000144863 650_7 $$2Other$$aNMDAR antibodies
000144863 650_7 $$2Other$$a600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit
000144863 773__ $$a10.17169/REFUBIUM-6306
000144863 8564_ $$uhttps://refubium.fu-berlin.de/bitstream/handle/fub188/2104/diss_j.leubner.pdf?sequence=1&isAllowed=y
000144863 8564_ $$uhttps://pub.dzne.de/record/144863/files/DZNE-2020-00288_Restricted.pdf
000144863 8564_ $$uhttps://pub.dzne.de/record/144863/files/DZNE-2020-00288_Restricted.pdf?subformat=pdfa$$xpdfa
000144863 909CO $$ooai:pub.dzne.de:144863$$pVDB
000144863 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2811472$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b0$$kDZNE
000144863 9131_ $$0G:(DE-HGF)POF3-342$$1G:(DE-HGF)POF3-340$$2G:(DE-HGF)POF3-300$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lErkrankungen des Nervensystems$$vDisease Mechanisms and Model Systems$$x0
000144863 9141_ $$y2017
000144863 920__ $$lyes
000144863 9201_ $$0I:(DE-2719)1810003$$kAG Prüß$$lAutoimmune Encephalopathies$$x0
000144863 980__ $$ahabil
000144863 980__ $$aVDB
000144863 980__ $$aI:(DE-2719)1810003
000144863 980__ $$aUNRESTRICTED