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  - Appeltshauser, Luise
A1  - Messinger, Julia
A1  - Starz, Katharina
A1  - Heinrich, David
A1  - Brunder, Anna-Michelle
A1  - Stengel, Helena
A1  - Fiebig, Bianca
A1  - Ayzenberg, Ilya
A1  - Birklein, Frank
A1  - Dresel, Christian
A1  - Dorst, Johannes
A1  - Dvorak, Florian
A1  - Grimm, Alexander
A1  - Joerk, Alexander
A1  - Leypoldt, Frank
A1  - Mäurer, Mathias
A1  - Merl, Patrick
A1  - Michels, Sebastian
A1  - Pitarokoili, Kalliopi
A1  - Rosenfeldt, Mathias
A1  - Sperfeld, Anne-Dorte
A1  - Weihrauch, Marc
A1  - Welte, Gabriel Simon
A1  - Sommer, Claudia
A1  - Doppler, Kathrin
T1  - Diabetes Mellitus Is a Possible Risk Factor for Nodo-paranodopathy With Antiparanodal Autoantibodies
JF  - Neurology: Neuroimmunology & Neuroinflammation
N2  - Background and Objectives 
Nodo-paranodopathies are peripheral neuropathies with dysfunction of the node of Ranvier. Affected patients who are seropositive for antibodies against adhesion molecules like contactin-1 and neurofascin show distinct clinical features and a disruption of the paranodal complex. An axoglial dysjunction is also a characteristic finding of diabetic neuropathy. Here, we aim to investigate a possible association of antibody-mediated nodo-paranodopathy and diabetes mellitus (DM).

Methods 
We retrospectively analyzed clinical data of 227 patients with chronic inflammatory demyelinating polyradiculoneuropathy and Guillain-Barré syndrome from multiple centers in Germany who had undergone diagnostic testing for antiparanodal antibodies targeting neurofascin-155, pan-neurofascin, contactin-1–associated protein 1, and contactin-1. To study possible direct pathogenic effects of antiparanodal antibodies, we performed immunofluorescence binding assays on human pancreatic tissue sections.

Results The frequency of DM was 33.3% in seropositive patients and thus higher compared with seronegative patients (14.1%, OR = 3.04, 95% CI = 1.31–6.80). The relative risk of DM in seropositive patients was 3.4-fold higher compared with the general German population. Seropositive patients with DM most frequently harbored anti–contactin-1 antibodies and had higher antibody titers than seropositive patients without DM. The diagnosis of DM preceded the onset of neuropathy in seropositive patients. No immunoreactivity of antiparanodal antibodies against pancreatic tissue was detected.

Discussion 
We report an association of nodo-paranodopathy and DM. Our results suggest that DM may be a potential risk factor for predisposing to developing nodo-paranodopathy and argue against DM being induced by the autoantibodies. Our findings set the basis for further research investigating underlying immunopathogenetic connections.
KW  - Diabetes mellitus
KW  - Nodo-parandopathy
KW  - Antiparanodal Autoantibodies
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300551
VL  - 9
IS  - 3
ER  -