Unsere Projekte

Wir untersuchen die Immunopathogenese der Multiplen Sklerose ausgehend von humanen Gewebe- und Blutproben und bearbeiten folgende Forschungsprojekte (Kurzbeschreibung in englischer Sprache):

Microenvironment of MS lesions

The complex interplay between invading immune cells and brain resident cells determines the development of MS lesions. To get further insight into this complex microenvironment, we established transcript profiles of dissected MS lesions from autopsy tissue using qPCR. Depending on the specific question we use frozen or archival FFPE tissue, dissect the whole lesion are or individual cells. Our studies gave insight into mechanisms of B cell survival and attraction, the role of astrocytes in both innate and adaptive immune reactions in the CNS.
We have quantified alterations of the extracellular matrix in active and inactive MS lesions, identified the components of the perivascular fibrosis of chronic lesions
and found that these products regulate monocytic chemokine production thus constituting a physical and biological barrier. Further we established the first miRNA profiles of MS lesions and could provide evidence that dysregulated miRNAs reduce the expression of CD47 unleashing macrophages. 

Current work is focused on the BAFF/APRIL system and on the regulation of remyelination in MS lesions.

Autoantibodies in MS patients

Autoantibodies are expected to be involved in the disease development of at least a proportion of MS patients. This is suggested by neuropathological examinations of MS lesions, the clinical response to plasmapheresis and recently observed effects of IgG of MS patients in an in vitro myelination system. We aim to identify novel targets of autoantibodies and to characterize the autoimmune response to candidate autoantigens.

One of the most studied candidate autoantigen is MOG.

While the picture is emerging that disease-relevant anti-MOG antibodies are largely absent in adult MS, anti-MOG Ig detected in a cell-bound assay is present in a proportion of children with demyelinating diseases. We found (in collaboration with A. Bar-Or and B. Banwell, Canadian Pediatric Study Group) that children with ADEM rapidly lose their autoantibodies, while children with MS tend to keep these antibodies. Thus, the persistence of autoantibodies to MOG might have prognostic relevance in childhood demyelination. Current work aims to identify epitopes recognized on human MOG.

To identify novel autoantigens recognized by adult MS patients we purified human myelin glycoproteins, separated them by 2D gel electrophoresis and identified the spots recognized by patients’ Ig with mass spectrometry. With this unbiased approach we identified two axoglial targets, neurofascin and contactin-2, located around the node of Ranvier (Figure 3). To elaborate the potential pathogenic relevance of such an autoimmune response we employed an EAE model (collaboration with C. Linington, now Glasgow, formerly MPI of Neurobiology). This showed that a mAb to neurofascin targets the Nodes of Ranvier and induces an axonal injury, while T cells specific for contactin-2/TAG-1 target an autoimmune inflammation preferentially to the grey matter. Current work aims at developing assays to detect antibodies to neurofascin and to determine their abundance in patients with MS and other inflammatory diseases of the nervous system.

Immunomodulatory treatment of MS patients

The possibilities to treat the relapsing remitting form of MS have increased in the last years and different substances are available. The understanding of the mechanism of action of immunomodulatory drugs given to MS patients and the monitoring of the biological response of the treated patients is a long-standing part of our research. We have analysed effects of Cop-1, IFN-ß, natalizumab, and rituximab on circulating immune cells of treated patients using flow cytometry, qPCR, and ELISPOT. This helps to optimize the individual therapy. Current research aims to understand effects of fingolimod on glial cells.
 
EN

Direktion

Prof. Dr.

Reinhard Hohlfeld

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Prof. Dr.

Martin Kerschensteiner

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Gruppenleiter

Prof. Dr.

Edgar Meinl

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