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  - 
TY  - JOUR
A1  - Karl, Franziska
A1  - Wußmann, Maximiliane
A1  - Kreß, Luisa
A1  - Malzacher, Tobias
A1  - Fey, Phillip
A1  - Groeber‐Becker, Florian
A1  - Üçeyler, Nurcan
T1  - Patient‐derived in vitro skin models for investigation of small fiber pathology
JF  - Annals of Clinical and Translational Neurology
N2  - Objective
To establish individually expandable primary fibroblast and keratinocyte cultures from 3‐mm skin punch biopsies for patient‐derived in vitro skin models to investigate of small fiber pathology.

Methods
We obtained 6‐mm skin punch biopsies from the calf of two patients with small fiber neuropathy (SFN) and two healthy controls. One half (3 mm) was used for diagnostic intraepidermal nerve fiber density (IENFD). From the second half, we isolated and cultured fibroblasts and keratinocytes. Cells were used to generate patient‐derived full‐thickness three‐dimensional (3D) skin models containing a dermal and epidermal component. Cells and skin models were characterized morphologically, immunocyto‐ and ‐histochemically (vimentin, cytokeratin (CK)‐10, CK 14, ki67, collagen1, and procollagen), and by electrical impedance.

Results
Distal IENFD was reduced in the SFN patients (2 fibers/mm each), while IENFD was normal in the controls (8 fibers/mm, 7 fibers/mm). Two‐dimensional (2D) cultured skin cells showed normal morphology, adequate viability, and proliferation, and expressed cell‐specific markers without relevant difference between SFN patient and healthy control. Using 2D cultured fibroblasts and keratinocytes, we obtained subject‐derived 3D skin models. Morphology of the 3D model was analogous to the respective skin biopsy specimens. Both, the dermal and the epidermal layer carried cell‐specific markers and showed a homogenous expression of extracellular matrix proteins.

Interpretation
Our protocol allows the generation of disease‐specific 2D and 3D skin models, which can be used to investigate the cross‐talk between skin cells and sensory neurons in small fiber pathology.
KW  - neurology
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201649
VL  - 6
IS  - 9
ER  -