TY  - JOUR
A1  - Doppler, Kathrin
A1  - Appeltshauser, Luise
A1  - Krämer, Heidrun H.
A1  - King Man Ng, Judy
A1  - Meinl, Edgar
A1  - Villmann, Carmen
A1  - Brophy, Peter
A1  - Dib-Hajj, Sulayman D.
A1  - Waxman, Stephen G.
A1  - Weishaupt, Andreas
A1  - Sommer, Claudia
T1  - Contactin-1 and Neurofascin-155/-186 Are Not Targets of Auto-Antibodies in Multifocal Motor Neuropathy
JF  - PLoS One
N2  - Multifocal motor neuropathy is an immune mediated disease presenting with multifocal muscle weakness and conduction block. IgM auto-antibodies against the ganglioside GM1 are detectable in about 50% of the patients. Auto-antibodies against the paranodal proteins contactin-1 and neurofascin-155 and the nodal protein neurofascin-186 have been detected in subgroups of patients with chronic inflammatory demyelinating polyneuropathy. Recently, auto-antibodies against neurofascin-186 and gliomedin were described in more than 60% of patients with multifocal motor neuropathy. In the current study, we aimed to validate this finding, using a combination of different assays for auto-antibody detection. In addition we intended to detect further auto-antibodies against paranodal proteins, specifically contactin-1 and neurofascin-155 in multifocal motor neuropathy patients’ sera. We analyzed sera of 33 patients with well-characterized multifocal motor neuropathy for IgM or IgG anti-contactin-1, anti-neurofascin-155 or -186 antibodies using enzyme-linked immunosorbent assay, binding assays with transfected human embryonic kidney 293 cells and murine teased fibers. We did not detect any IgM or IgG auto-antibodies against contactin-1, neurofascin-155 or -186 in any of our multifocal motor neuropathy patients. We conclude that auto-antibodies against contactin-1, neurofascin-155 and -186 do not play a relevant role in the pathogenesis in this cohort with multifocal motor neuropathy.
KW  - motor proteins
KW  - enzyme-linked immunoassays
KW  - binding analysis
KW  - neuropathy
KW  - nerve fibers
KW  - cell binding assay
KW  - antibodies
KW  - enzyme assays
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-126156
VL  - 10
IS  - 7
ER  - 
TY  - JOUR
A1  - Üçeyler, Nurcan
A1  - Schröter, Nils
A1  - Kafke, Waldemar
A1  - Kramer, Daniela
A1  - Wanner, Christoph
A1  - Weidemann, Frank
A1  - Sommer, Claudia
T1  - Skin Globotriaosylceramide 3 Load Is Increased in Men with Advanced Fabry Disease
JF  - PLoS ONE
N2  - Background
The X-chromosomally linked life-limiting Fabry disease (FD) is associated with deposits of the sphingolipid globotriaosylceramide 3 (Gb3) in various tissues. Skin is easily accessible and may be used as an additional diagnostic and follow-up medium. Our aims were to visualize skin Gb3 deposits in FD patients applying immunofluorescence and to determine if cutaneous Gb3 load correlates with disease severity.

Methods
At our Fabry Center for Interdisciplinary Therapy we enrolled 84 patients with FD and 27 healthy controls. All subjects underwent 5-mm skin punch biopsy at the lateral lower leg and the back. Skin samples were processed for immunohistochemistry using antibodies against CD77 (i.e. Gb3). Cutaneous Gb3 deposition was quantified in a blinded manner and correlated to clinical data.

Results
We found that Gb3 load was higher in distal skin of male FD patients compared to healthy controls (p<0.05). Men (p<0.01) and women (p<0.05) with a classic FD phenotype had higher distal skin Gb3 load than healthy controls. Men with advanced disease as reflected by impaired renal function, and men and women with small fiber neuropathy had more Gb3 deposits in distal skin samples than males with normal renal function (p<0.05) and without small fiber neuropathy. Gb3 deposits were not different between patients with and without enzyme replacement therapy.

Conclusions
Immunofluorescence on minimally invasive skin punch biopsies may be useful as a tool for assessment and follow-up in FD patients.
KW  - biopsy
KW  - neuropathy
KW  - Fabry disease
KW  - renal system
KW  - immunofluorescence
KW  - enzyme replacement therapy
KW  - skin diseases
KW  - nerve fibers
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-178856
VL  - 11
IS  - 11
ER  -