TY  - JOUR
A1  - Rauschenberger, Vera
A1  - von Wardenburg, Niels
A1  - Schaefer, Natascha
A1  - Ogino, Kazutoyo
A1  - Hirata, Hiromi
A1  - Lillesaar, Christina
A1  - Kluck, Christoph J.
A1  - Meinck, Hans‐Michael
A1  - Borrmann, Marc
A1  - Weishaupt, Andreas
A1  - Doppler, Kathrin
A1  - Wickel, Jonathan
A1  - Geis, Christian
A1  - Sommer, Claudia
A1  - Villmann, Carmen
T1  - Glycine Receptor Autoantibodies Impair Receptor Function and Induce Motor Dysfunction
JF  - Annals of Neurology
N2  - Objective
Impairment of glycinergic neurotransmission leads to complex movement and behavioral disorders. Patients harboring glycine receptor autoantibodies suffer from stiff‐person syndrome or its severe variant progressive encephalomyelitis with rigidity and myoclonus. Enhanced receptor internalization was proposed as the common molecular mechanism upon autoantibody binding. Although functional impairment of glycine receptors following autoantibody binding has recently been investigated, it is still incompletely understood.

Methods
A cell‐based assay was used for positive sample evaluation. Glycine receptor function was assessed by electrophysiological recordings and radioligand binding assays. The in vivo passive transfer of patient autoantibodies was done using the zebrafish animal model.

Results
Glycine receptor function as assessed by glycine dose–response curves showed significantly decreased glycine potency in the presence of patient sera. Upon binding of autoantibodies from 2 patients, a decreased fraction of desensitized receptors was observed, whereas closing of the ion channel remained fast. The glycine receptor N‐terminal residues \(^{29}\)A to \(^{62}\)G were mapped as a common epitope of glycine receptor autoantibodies. An in vivo transfer into the zebrafish animal model generated a phenotype with disturbed escape behavior accompanied by a reduced number of glycine receptor clusters in the spinal cord of affected animals.

Interpretation
Autoantibodies against the extracellular domain mediate alterations of glycine receptor physiology. Moreover, our in vivo data demonstrate that the autoantibodies are a direct cause of the disease, because the transfer of human glycine receptor autoantibodies to zebrafish larvae generated impaired escape behavior in the animal model compatible with abnormal startle response in stiff‐person syndrome or progressive encephalitis with rigidity and myoclonus patients.
KW  - glycine receptor autoantibodies
KW  - behavioral disorders
KW  - neurology
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-216005
VL  - 88
IS  - 3
SP  - 544
EP  - 561
ER  - 
TY  - JOUR
A1  - Rodriguez-Rozada, Silvia
A1  - Frantz, Stefan
A1  - Tovote, Philip
T1  - Cardiac optogenetics: regulating brain states via the heart
JF  - Signal Transduction and Targeted Therapy
N2  - No abstract available.
KW  - cardiology
KW  - neurology
KW  - neuroscience
KW  - systems biology
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357625
VL  - 8
ER  - 
TY  - JOUR
A1  - Stengel, Helena
A1  - Vural, Atay
A1  - Brunder, Anna-Michelle
A1  - Heinius, Annika
A1  - Appeltshauser, Luise
A1  - Fiebig, Bianca
A1  - Giese, Florian
A1  - Dresel, Christian
A1  - Papagianni, Aikaterini
A1  - Birklein, Frank
A1  - Weis, Joachim
A1  - Huchtemann, Tessa
A1  - Schmidt, Christian
A1  - Körtvelyessy, Peter
A1  - Villmann, Carmen
A1  - Meinl, Edgar
A1  - Sommer, Claudia
A1  - Leypoldt, Frank
A1  - Doppler, Kathrin
T1  - Anti–pan-neurofascin IgG3 as a marker of fulminant autoimmune neuropathy
JF  - Neurology: Neuroimmunology & Neuroinflammation
N2  - Objective 
To identify and characterize patients with autoantibodies against different neurofascin (NF) isoforms.

Methods 
Screening of a large cohort of patient sera for anti-NF autoantibodies by ELISA and further characterization by cell-based assays, epitope mapping, and complement binding assays.

Results 
Two different clinical phenotypes became apparent in this study: The well-known clinical picture of subacute-onset severe sensorimotor neuropathy with tremor that is known to be associated with IgG4 autoantibodies against the paranodal isoform NF-155 was found in 2 patients. The second phenotype with a dramatic course of disease with tetraplegia and almost locked-in syndrome was associated with IgG3 autoantibodies against nodal and paranodal isoforms of NF in 3 patients. The epitope against which these autoantibodies were directed in this second phenotype was the common Ig domain found in all 3 NF isoforms. In contrast, anti–NF-155 IgG4 were directed against the NF-155–specific Fn3Fn4 domain. The description of a second phenotype of anti–NF-associated neuropathy is in line with some case reports of similar patients that were published in the last year.

Conclusions 
Our results indicate that anti–pan-NF-associated neuropathy differs from anti–NF-155-associated neuropathy, and epitope and subclass play a major role in the pathogenesis and severity of anti–NF-associated neuropathy and should be determined to correctly classify patients, also in respect to possible differences in therapeutic response.
KW  - neurology
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202462
VL  - 6
IS  - 5
ER  -