TY  - JOUR
A1  - Meyer zu Hörste, Gerd
A1  - Cordes, Steffen
A1  - Mausberg, Anne K.
A1  - Zozulya, Alla L.
A1  - Wessig, Carsten
A1  - Sparwasser, Tim
A1  - Mathys, Christian
A1  - Wiendl, Heinz
A1  - Hartung, Hans-Peter
A1  - Kieseier, Bernd C.
T1  - FoxP3+Regulatory T Cells Determine Disease Severity in Rodent Models of Inflammatory Neuropathies
JF  - PLOS ONE
N2  - Inflammatory neuropathies represent disabling human autoimmune disorders with considerable disease variability. Animal models provide insights into defined aspects of their disease pathogenesis. Forkhead box P3 (FoxP3)+ regulatory T lymphocytes (Treg) are anti-inflammatory cells that maintain immune tolerance and counteract tissue damage in a variety of immune-mediated disorders. Dysfunction or a reduced frequency of Tregs have been associated with different human autoimmune disorders. We here analyzed the functional relevance of Tregs in determining disease manifestation and severity in murine models of autoimmune neuropathies. We took advantage of the DEREG mouse system allowing depletion of Treg with high specificity as well as anti-CD25 directed antibodies to deplete Tregs in mice in actively induced experimental autoimmune neuritis (EAN). Furthermore antibody-depletion was performed in an adoptive transfer model of chronic neuritis. Early Treg depletion increased clinical EAN severity both in active and adoptive transfer chronic neuritis. This was accompanied by increased proliferation of myelin specific T cells and histological signs of peripheral nerve inflammation. Late stage Treg depletion after initial disease manifestation however did not exacerbate inflammatory neuropathy symptoms further. We conclude that Tregs determine disease severity in experimental autoimmune neuropathies during the initial priming phase, but have no major disease modifying function after disease manifestation. Potential future therapeutic approaches targeting Tregs should thus be performed early in inflammatory neuropathies.
KW  - Guillain-Barre-Syndrome
KW  - regulatory cells
KW  - C57BL/6 mice
KW  - demyelinating polyradiculoneuropathy
KW  - cytokines
KW  - pathogenesis
KW  - polyneuropathy
KW  - enteropathy
KW  - peptide
KW  - experimental autoimmune neuritis
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-115239
VL  - 9
IS  - 10
ER  - 
TY  - JOUR
A1  - Brandt, Alexander U.
A1  - Zimmermann, Hanna
A1  - Kaufhold, Falko
A1  - Promesberger, Julia
A1  - Schippling, Sven
A1  - Finis, David
A1  - Aktas, Orhan
A1  - Geis, Christian
A1  - Ringelstein, Marius
A1  - Ringelstein, E. Bernd
A1  - Hartung, Hans-Peter
A1  - Paul, Friedemann
A1  - Kleffner, Ilka
A1  - Dörr, Jan
T1  - Patterns of Retinal Damage Facilitate Differential Diagnosis between Susac Syndrome and MS
JF  - PLoS One
N2  - Susac syndrome, a rare but probably underdiagnosed combination of encephalopathy, hearing loss, and visual deficits due to branch retinal artery occlusion of unknown aetiology has to be considered as differential diagnosis in various conditions. Particularly, differentiation from multiple sclerosis is often challenging since both clinical presentation and diagnostic findings may overlap. Optical coherence tomography is a powerful and easy to perform diagnostic tool to analyse the morphological integrity of retinal structures and is increasingly established to depict characteristic patterns of retinal pathology in multiple sclerosis. Against this background we hypothesised that differential patterns of retinal pathology facilitate a reliable differentiation between Susac syndrome and multiple sclerosis. In this multicenter cross-sectional observational study optical coherence tomography was performed in nine patients with a definite diagnosis of Susac syndrome. Data were compared with age-, sex-, and disease duration-matched relapsing remitting multiple sclerosis patients with and without a history of optic neuritis, and with healthy controls. Using generalised estimating equation models, Susac patients showed a significant reduction in either or both retinal nerve fibre layer thickness and total macular volume in comparison to both healthy controls and relapsing remitting multiple sclerosis patients. However, in contrast to the multiple sclerosis patients this reduction was not distributed over the entire scanning area but showed a distinct sectorial loss especially in the macular measurements. We therefore conclude that patients with Susac syndrome show distinct abnormalities in optical coherence tomography in comparison to multiple sclerosis patients. These findings recommend optical coherence tomography as a promising tool for differentiating Susac syndrome from MS.
KW  - optical coherence tomography
KW  - vasculopathy
KW  - artery occlusion
KW  - hearing loss
KW  - microangiopathy
KW  - brain
KW  - endotheliopathy
KW  - antibodies
KW  - multiple-sclerosis
KW  - retinocochleocerebral
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134013
VL  - 7
IS  - 6
ER  -