A5009443014- Multiple Sclerosis Research Studies
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Neuroinflammation and Neurodegeneration Mechanisms
- Cellular transport and secretion
- Peripheral Neuropathies and Disorders
- Monoclonal and Polyclonal Antibodies Research
- Parkinson's Disease Mechanisms and Treatments
- Immune Response and Inflammation
- Nuclear Receptors and Signaling
- Autoimmune Neurological Disorders and Treatments
- Systemic Lupus Erythematosus Research
- Polyomavirus and related diseases
- Ubiquitin and proteasome pathways
- Psoriasis: Treatment and Pathogenesis
- Sphingolipid Metabolism and Signaling
- Neurogenesis and neuroplasticity mechanisms
- Amyotrophic Lateral Sclerosis Research
- Cholinesterase and Neurodegenerative Diseases
- Autoimmune and Inflammatory Disorders Research
- Bacterial Infections and Vaccines
- Reproductive System and Pregnancy
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Ocular Diseases and Behçet’s Syndrome
- T-cell and Retrovirus Studies
Technical University of Munich
2013-2024
Munich Cluster for Systems Neurology
2016-2023
Charité - Universitätsmedizin Berlin
2021
University of California, San Francisco
2014-2020
Klinikum rechts der Isar
2008-2020
John Radcliffe Hospital
2020
University of Oxford
2020
Monash University
2016
University of Duisburg-Essen
2016
Klinikum Ingolstadt
2016
Abstract Objective Clinical studies indicate that anti‐CD20 B‐cell depletion may be an effective multiple sclerosis (MS) therapy. We investigated mechanisms of anti‐CD20‐mediated immune modulation using 2 paradigms experimental autoimmune encephalomyelitis (EAE). Methods Murine EAE was induced by recombinant myelin oligodendrocyte glycoprotein (rMOG), a model in which B cells are considered to contribute pathogenically, or MOG peptide (p)35‐55, does not require cells. Results In rMOG, became...
Demyelination in MS disrupts nerve signals and contributes to axon degeneration. While remyelination promises restore lost function, it remains unclear whether will prevent axonal loss. Inflammatory demyelination is accompanied by significant neuronal loss the experimental autoimmune encephalomyelitis (EAE) mouse model evidence for this complicated ongoing inflammation, degeneration possible remyelination. Demonstrating functional significance of necessitates selectively altering timing...
To evaluate the influence of dimethyl fumarate (DMF, Tecfidera) treatment multiple sclerosis (MS) on leukocyte and lymphocyte subsets.Peripheral blood subsets, including CD3(+), CD4(+), CD8(+) T cells; CD19(+) B CD56(+) natural killer (NK) cells, were obtained at baseline monitored 3 months, 6 12 months after initiation DMF treatment.Total counts diminished therapy. At had decreased by 50.1% (p < 0.0001) below lower limit normal (LLN) in one-half patients. CD3(+) fell 44.2% 0.0001). Among...
Recent years have substantially broadened our view on the pathogenesis of multiple sclerosis (MS). While earlier concepts focused predominantly T lymphocytes as key cell type to mediate inflammatory damage within central nervous system (CNS) lesions, emerging evidence suggests that B may play a comparably important role both precursors antibody-secreting plasma cells and antigen-presenting (APCs) for activation cells. With greater appreciation this pathogenic B-cell function in MS,...
Significance B cell depletion via anti-CD20 monoclonal antibodies is a novel, highly efficient therapy for multiple sclerosis (MS). In murine MS model, we investigated three mechanistic questions that cannot be addressed in humans. First, established fraction of mature cells the spleen resistant to anti-CD20. Second, determined that, after cessation treatment, splenic and bone-marrow reconstitute parallel, substantially preceding reappearance blood. Third, observed model involving activated...
Multiple sclerosis (MS) disease risk is associated with reduced sun-exposure. This study assessed the relationship between measures of sun exposure (vitamin D [vitD], latitude) and MS severity in setting two multicenter cohort studies (nNationMS = 946, nBIONAT 990). Additionally, effect-modification by medication photosensitivity-associated MC1R variants was assessed. High serum vitD a score (MSSS), for relapses, lower disability accumulation over time. Low latitude higher vitD, MSSS, fewer...
Abstract Background Clinical trials evaluating anti-CD20-mediated B-cell depletion in multiple sclerosis (MS) and neuromyelitis optica (NMO) generated encouraging results. Our recent studies the MS model experimental autoimmune encephalomyelitis (EAE) attributed clinical benefit to extinction of activated B-cells, but cautioned that naïve B-cells may be undesirable. We elucidated regulatory role un-activated EAE investigated whether anti-CD20 collaterally diminish properties treatment...
Ectopic lymphoid tissues (ELT) can be found in multiple sclerosis (MS) and other organ-specific inflammatory conditions. Whether ELT the meninges of central nervous system (CNS) autoimmune disease exhibit local germinal center (GC) activity remains unknown. In an experimental encephalomyelitis model CNS autoimmunity, we activation-induced cytidine deaminase, a GC-defining enzyme, meningeal (mELT) densely populated by B T cells. To determine GC mELT, excised aggregates using laser capture...
Progressive multifocal leukoencephalopathy (PML), which is caused by the John Cunningham virus (JCV), a rare brain disease that results in persistent neurologic disability or death. In multiple sclerosis (MS), PML major concern patients treated with natalizumab, and treatment duration (more than 2 years), preceding immunosuppression, JCV antibody serostatus are identified risk factors, used for stratification, patient monitoring, counseling.
Natalizumab, which binds very late antigen‐4 (VLA‐4), is a potent therapy for multiple sclerosis (MS). Studies have focused primarily upon its capacity to interfere with T‐cell migration into the central nervous system (CNS). B cells are important in MS pathogenesis and express high levels of VLA‐4. Here, we report that selective inhibition VLA‐4 expression on impedes CNS accumulation cells, recruitment Th17 macrophages, reduces susceptibility experimental autoimmune encephalomyelitis. These...
Retinal optical coherence tomography (OCT) is a clinical and research tool in multiple sclerosis, where it has shown significant retinal nerve fiber (RNFL) ganglion cell (RGC) layer thinning, while postmortem studies have reported RGC loss. Although pathology experimental autoimmune encephalomyelitis (EAE) been described, comparative OCT among EAE models are scarce. Furthermore, the best practices for implementation of lab, especially with afoveate animals like rodents, remain undefined. We...
<h3>Objective</h3> To study intrathecal B-cell activity in leucine-rich, glioma-inactivated 1 (LGI1) antibody encephalitis. In patients with LGI1 antibodies, the lack of CSF lymphocytosis or oligoclonal bands and serum-predominant antibodies suggests a peripherally initiated immune response. However, it is unknown whether B cells within CNS contribute to ongoing pathogenesis <h3>Methods</h3> Paired peripheral blood (PB) mononuclear were collected from 6 encephalitis 2 other neurologic...
Abstract B cells contribute to chronic inflammatory conditions as source of antibody-secreting plasma and antigen-presenting activating T cells, making anti-CD20-mediated cell depletion a widely used therapeutic option. or subsets may, however, exert regulatory effects, while date, the immunological and/or clinical impact these observations remained unclear. We found that in multiple sclerosis (MS) patients, contain features their removal enhanced activity monocytes. Using co-culture system,...
To investigate whether anti-CD20 B-cell-depleting monoclonal antibodies (ɑCD20 mAbs) inhibit the formation or retention of meningeal ectopic lymphoid tissue (mELT) in a murine model multiple sclerosis (MS).We used spontaneous chronic experimental autoimmune encephalomyelitis (EAE) mice with mutant T-cell and B-cell receptors specific for myelin oligodendrocyte glycoprotein (MOG), which develop inflammatory infiltrates resembling those described MS. ɑCD20 mAbs were administered either...
<h3>Objective:</h3> To investigate the role of very late antigen-4 (VLA-4) on regulatory B cells (Breg) in CNS autoimmune disease. <h3>Methods:</h3> Experimental encephalomyelitis (EAE) was induced mice selectively deficient for VLA-4 (CD19cre/α4<sup>f/f</sup>) by immunization with myelin oligodendrocyte glycoprotein (MOG) peptide (p)35–55 or recombinant human (rh) MOG protein. B-cell and T-cell populations were examined flow cytometry immunohistochemistry. Breg evaluated intracellular IL-10...
Clinical trials revealed that systemic administration of B-cell-depleting anti-CD20 antibodies can hold lesion formation in the early relapsing-remitting phase multiple sclerosis (MS). Throughout secondary-progressive (SP) course MS, pathogenic B cells may, however, progressively replicate within central nervous system (CNS) itself, which is largely inaccessible to treatment. Utilizing murine MS model experimental autoimmune encephalomyelitis, we show intrathecal (i.t.) alone very...
Bacterial and viral infections have long been implicated in pathogenesis progression of multiple sclerosis (MS). Incidence severity its animal model experimental autoimmune encephalomyelitis (EAE) can be enhanced by concomitant administration pertussis toxin (PTx), the major virulence factor Bordetella pertussis. Its adjuvant effect at time immunization with myelin antigen is attributed to an unspecific activation facilitated migration immune cells across blood brain barrier into central...
<h3>Background and Objectives</h3> To investigate whether the formation or retention of meningeal ectopic lymphoid tissue (mELT) can be inhibited by sphingosine 1-phosphate receptor 1,5 modulator siponimod (BAF312) in a murine model multiple sclerosis (MS). <h3>Methods</h3> A spontaneous chronic experimental autoimmune encephalomyelitis (EAE) model, featuring inflammatory infiltrates resembling those MS, was used. prevent treat EAE, administered daily starting either before EAE onset at peak...
MS is an inflammatory CNS disorder, which typically occurs in early adulthood and rarely children. Here we tested whether functional maturation of innate immune cells may determine susceptibility to autoimmune disease EAE. Two‐week‐old mice were resistant active EAE, causes fulminant paralysis adult mice; this resistance was associated with impaired development Th1 Th17 cells. Resistant, young had higher frequencies myeloid‐derived suppressor plasma‐cytoid DCs. Furthermore, myeloid APCs B...
The factors that drive progression in multiple sclerosis (MS) remain obscure. Identification of key properties meningeal inflammation will contribute to a better understanding the mechanisms and how prevent it.Applying single-cell RNA sequencing, we compared gene expression profiles immune cells from ectopic lymphoid tissue (mELT) with those secondary organs (SLOs) spontaneous chronic experimental autoimmune encephalomyelitis (EAE), an animal model MS.Generally, mELT contained same cell...