A5061814062- Multiple Sclerosis Research Studies
- Immune Cell Function and Interaction
- Neuroinflammation and Neurodegeneration Mechanisms
- T-cell and B-cell Immunology
- Autoimmune Neurological Disorders and Treatments
- Immunotherapy and Immune Responses
- Peripheral Neuropathies and Disorders
- Polyomavirus and related diseases
- Single-cell and spatial transcriptomics
- Heat shock proteins research
- Vasculitis and related conditions
- Toxin Mechanisms and Immunotoxins
- Cytomegalovirus and herpesvirus research
- Immune cells in cancer
- RNA Interference and Gene Delivery
- Cell Adhesion Molecules Research
- CAR-T cell therapy research
- RNA regulation and disease
- Retinal and Optic Conditions
- Genetics and Neurodevelopmental Disorders
- Barrier Structure and Function Studies
- Plant Virus Research Studies
- Full-Duplex Wireless Communications
- Exercise and Physiological Responses
- Bacterial Infections and Vaccines
University Hospital Münster
2016-2025
University of Münster
2016-2025
John Wiley & Sons (United States)
2023
Hudson Institute
2023
Liechtenstein Institute
2023
Heinrich Heine University Düsseldorf
2016-2022
Otto-von-Guericke University Magdeburg
2022
University Hospital Magdeburg
2022
University Clinic for Nephrology and Hypertension, Diabetology and Endocrinology
2022
Rockefeller University
2022
Abstract Detergent-soluble membrane vesicles are actively released by human pancreas (Colo−/Colo+) and colon (CX−/CX+) carcinoma sublines, differing in their capacity to present heat shock protein 70 (Hsp70)/Bag-4 on plasma membranes. Floating properties, acetylcholine esterase activity, composition characterized them as exosomes. An enrichment of Rab-4 documented intracellular transport route from early endosomes the membrane. After solubilization, comparable amounts cytosolic proteins,...
Abstract Cerebrospinal fluid (CSF) protects the central nervous system (CNS) and analyzing CSF aids diagnosis of CNS diseases, but our understanding leukocytes remains superficial. Here, using single cell transcriptomics, we identify a specific location-associated composition transcriptome leukocytes. Multiple sclerosis (MS) – an autoimmune disease increases transcriptional diversity in blood, type including higher abundance cytotoxic phenotype T helper cells. An analytical approach, named...
Significance The importance of natural killer (NK) cells in the control autoimmunity has recently attracted considerable attention. current study revealed NK as additional players controlling T-cell activity CNS autoimmunity. NK-mediated multiple sclerosis (MS) is dysregulated and caused by impaired DNAX accessory molecule-1/CD155 interaction between CD4 + T cells. Therapeutic immune modulation IL-2 receptor with daclizumab, which just successfully passed a phase III relapsing-remitting MS,...
Abstract Background Comprehensive data on the cerebrospinal fluid (CSF) profile in patients with COVID-19 and neurological involvement from large-scale multicenter studies are missing so far. Objective To analyze systematically CSF COVID-19. Methods Retrospective analysis of 150 lumbar punctures 127 PCR-proven symptoms seen at 17 European university centers Results The most frequent pathological finding was blood-CSF barrier (BCB) dysfunction (median QAlb 11.4 [6.72–50.8]), which present...
<h3>Background and Objectives</h3> To determine the real-world use of rituximab in autoimmune encephalitis (AE) to correlate treatment with long-term outcome. <h3>Methods</h3> Patients NMDA receptor (NMDAR)-AE, leucine-rich glioma-inactivated-1 (LGI1)- AE, contactin-associated protein-like-2 (CASPR2)-AE, or glutamic acid decarboxylase 65 (GAD65) disease from GErman Network for Research on AuToimmune Encephalitis who had received at least 1 dose a control cohort non–rituximab-treated patients...
Anti-IgLON5 disease is a newly defined clinical entity characterized by progressive course with high disability and mortality rate. While precise pathogenetic mechanisms remain unclear, features characteristic of both autoimmune neurodegenerative diseases were reported. Data on immunotherapy are limited, its efficacy remains controversial. In this study, we retrospectively investigated an anti-IgLON5 cohort special focus clinical, serological genetic predictors the response long-term...
Abstract Purpose: The 14 amino acid sequence (aa450–463) TKDNNLLGRFELSG (TKD) of heat shock protein 70 (Hsp70) was identified as a tumor-selective recognition structure for natural killer (NK) cells. Incubation peripheral blood lymphocyte cells with TKD plus low-dose interleukin 2 (IL-2) enhances the cytolytic activity NK against Hsp70 membrane-positive tumors, in vitro and vivo. These data encouraged us to test tolerability, feasibility, safety TKD-activated clinical Phase I trial....
Cell surface-bound heat shock protein 70 (Hsp70) renders tumor cells more sensitive to the cytolytic attack mediated by natural killer (NK) cells. A 14-amino acid Hsp70 sequence, termed TKD (TKDNNLLGRFELSG, aa450–463) could be identified as extracellular localized recognition site for NK Here, we show affinity chromatography that both, full-length Hsp70-protein and Hsp70-peptide TKD, specifically bind a 32-kDa derived from cell lysates. The serine protease granzyme B was uncovered...
Full-length Hsp70 protein (Hsp70) and the C-terminal domain of (Hsp70C) both stimulate cytolytic activity naive natural killer (NK) cells against Hsp70-positive tumor target cells. Here, we describe characterization Hsp70-NK cell interaction with binding studies using human NK line YT. Binding recombinant to YT is demonstrated by immunofluorescence studies. A phenotypic revealed that none recently described HSP-receptors (alpha2-macroglobulin receptor CD91, Toll-like receptors 2, 4, 9, CD14)...
The focus of this study is the characterization human T cell blood-brain barrier migration and corresponding molecular trafficking signatures. We examined peripheral blood cerebrospinal fluid immune cells from patients under long-term anti-very late antigen-4 (VLA-4)/natalizumab therapy (LTNT) CNS specimens. LTNT patients' exhibited healthy central-/effector-memory ratios, but lacked CD49d showed enhanced myeloma adhesion molecule (MCAM) expression. led to an increase PSGL-1 expression on...
To evaluate the effect of dimethyl fumarate (DMF; Tecfidera, Biogen, Weston, MA) on CD4(+) and CD8(+) T cell subsets in patients with multiple sclerosis (MS).Peripheral lymphocyte subsets, including memory cells helper (TH) TH1, TH2, TH17, peripheral regulatory (pTreg) subpopulations were analyzed before 6 months after onset DMF treatment.CD4(+) preferentially decreased compared to naive populations. Within population, frequencies TH1 decreased, whereas those TH2 increased TH17 remained...
Aberrant immune responses represent the underlying cause of central nervous system (CNS) autoimmunity, including multiple sclerosis (MS). Recent evidence implicated crosstalk between coagulation and immunity in CNS autoimmunity. Here we identify factor XII (FXII), initiator intrinsic cascade kallikrein-kinin system, as a specific cell modulator. High levels FXII activity are present plasma MS patients during relapse. Deficiency or pharmacologic blockade renders mice less susceptible to...
The feeling of “body ownership” may be experimentally investigated by perceptual illusions. “rubber hand illusion” (RHI) leads human subjects to experience an artificial as their own. According functional imaging, the ventral premotor cortex (PMv) plays a key role in integration multisensory inputs allowing “incorporation” rubber into body representation. However, causal structure–function relationships can only obtained lesion studies. Here, we tested RHI 70 stroke patients and 40...
Abstract Neuroinflammation is often associated with blood-brain-barrier dysfunction, which contributes to neurological tissue damage. Here, we reveal the pathophysiology of Susac syndrome (SuS), an enigmatic neuroinflammatory disease central nervous system (CNS) endotheliopathy. By investigating immune cells from blood, cerebrospinal fluid, and CNS SuS patients, demonstrate oligoclonal expansion terminally differentiated activated cytotoxic CD8 + T (CTLs). Neuropathological data derived both...
Environmental conditions (eg, latitude) play a critical role in the susceptibility and severity of many autoimmune disorders, including multiple sclerosis (MS). Here, we investigated mechanisms underlying beneficial effects immune regulatory processes induced skin by moderate ultraviolet B (UVB) radiation on central nervous system (CNS) autoimmunity.Effects UVB light were analyzed murine model CNS autoimmunity (experimental encephalomyelitis). Additionally, patients with relapsing-remitting...
Inhibition of a mitochondrial enzyme during multiple sclerosis treatment modulates antigen-specific T cell responses in an affinity-dependent fashion.
Background: Parkinson’s disease (PD) is a common neurodegenerative disorder. The contribution of the immune system to its pathogenesis remains incompletely understood. Methods: In this study, we performed comprehensive cell profiling in cerebrospinal fluid (CSF) and peripheral blood (PB) PD patients. Ten patients were diagnosed according brain bank criteria underwent detailed clinical examination, magnetic resonance imaging, PB CSF by multiparameter flow cytometry, cytokine chemokine...
Abstract Objective Autoimmune encephalitis is most frequently associated with anti‐ NMDAR autoantibodies. Their pathogenic relevance has been suggested by passive transfer of patients' cerebrospinal fluid ( CSF ) in mice vivo. We aimed to analyze the intrathecal plasma cell repertoire, identify autoantibody‐producing clones, and characterize their antibody signatures recombinant form. Methods Patients recent onset typical were subjected flow cytometry analysis peripheral immune response...
The enzymes gelatinase A/matrix metalloproteinase-2 (MMP-2) and B/MMP-9 are essential for induction of neuroinflammatory symptoms in experimental autoimmune encephalomyelitis (EAE), a mouse model multiple sclerosis (MS); the absence these enzymes, disease does not develop. We therefore investigated cellular sources relative contributions MMP-2 MMP-9 to at early stages EAE induction. demonstrated that from an immune cell source is required initial infiltration leukocytes into central nervous...
To characterize changes in myeloid and lymphoid innate immune cells patients with relapsing-remitting multiple sclerosis (MS) during a 6-month follow-up after alemtuzumab treatment.Circulating including (ILCs) were analyzed before 6 12 months onset of treatment. Furthermore, potential effect on granulocyte-macrophage colony-stimulating factor (GM-CSF) interleukin (IL)-23 production by natural killer (NK) cell cytolytic activity was determined.In comparison to CD4+ T lymphocytes, subsets MS...
Based on the advances in treatment of multiple sclerosis (MS), currently available disease-modifying treatments (DMT) have positively influenced disease course MS. However, efficacy DMT is highly variable and increasing comes with a more severe risk profile. Hence, unmet need for safer selective remains. Specifically restoring immune tolerance towards myelin antigens may provide an attractive alternative. In this respect, antigen-specific tolerisation autologous tolerogenic dendritic cells...