A5051643302- Multiple Sclerosis Research Studies
- Neuroinflammation and Neurodegeneration Mechanisms
- CNS Lymphoma Diagnosis and Treatment
- T-cell and B-cell Immunology
- Autoimmune Neurological Disorders and Treatments
- Immunotherapy and Immune Responses
- Peripheral Neuropathies and Disorders
- Immune Cell Function and Interaction
- Single-cell and spatial transcriptomics
- Cytomegalovirus and herpesvirus research
- Vasculitis and related conditions
- Polyomavirus and related diseases
- interferon and immune responses
- IL-33, ST2, and ILC Pathways
- Cytokine Signaling Pathways and Interactions
- Systemic Lupus Erythematosus Research
- Cancer Immunotherapy and Biomarkers
- Reproductive System and Pregnancy
- Mathematical Biology Tumor Growth
- melanin and skin pigmentation
- Barrier Structure and Function Studies
- Hair Growth and Disorders
- Immune Response and Inflammation
- Fungal Infections and Studies
- Amyloidosis: Diagnosis, Treatment, Outcomes
University of Münster
2016-2025
University Hospital Münster
2016-2025
John Wiley & Sons (United States)
2023
Hudson Institute
2023
Liechtenstein Institute
2023
Heinrich Heine University Düsseldorf
2016-2022
Düsseldorf University Hospital
2016-2021
The University of Sydney
2021
Klinik und Poliklinik für Neurologie
2020
Essen University Hospital
2019
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,...
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...
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...
Inhibition of a mitochondrial enzyme during multiple sclerosis treatment modulates antigen-specific T cell responses in an affinity-dependent fashion.
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...
Abstract Alemtuzumab is a monoclonal antibody that causes rapid depletion of CD52-expressing immune cells. It has proven to be highly efficacious in active relapsing–remitting multiple sclerosis; however, the high risk secondary autoimmune disorders greatly complicated its use. Thus, deeper insight into pathophysiology autoimmunity and potential biomarkers urgently needed. The most critical time points decision-making process for alemtuzumab therapy are before or at Month 12, where ability...
Peripheral central nervous system (CNS)–infiltrating lymphocytes are a hallmark of relapsing-remitting multiple sclerosis. Tissue-resident memory T cells (T RM ) not only populate the healthy CNS parenchyma but also suspected to contribute sclerosis pathology. Because cerebrospinal fluid (CSF), unlike parenchyma, is accessible for diagnostics, we evaluated whether human CSF, apart from infiltrating cells, contains and CNS-resident myeloid draining or border tissues. Using deep generative...
One of the biggest challenges in managing multiple sclerosis is heterogeneity clinical manifestations and progression trajectories. It still remains to be elucidated whether this reflected by discrete immune signatures blood as a surrogate disease pathophysiology. Accordingly, individualized treatment selection based on immunobiological principles not feasible. Using two independent multicentric longitudinal cohorts patients with early ( n = 309 discovery 232 validation), we were able...
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 Although CSF analysis routinely enables the diagnosis of neurological diseases, it is mainly used for gross distinction between infectious, autoimmune inflammatory, and degenerative disorders CNS. To investigate, whether a multi-dimensional cellular blood characterization can support clinically similar we analysed 546 patients with neuroinflammatory, degenerative, or vascular conditions in cross-sectional retrospective study. By combining feature selection dimensionality reduction...
Although the CNS is immune privileged, continuous search for pathogens and tumours by cells within indispensable. Thus, distinct immune-cell populations also cross blood-brain barrier independently of inflammation/under homeostatic conditions. It was previously shown that effector memory T populate healthy parenchyma in humans and, independently, CCR5-expressing lymphocytes as well CCR5 ligands are enriched patients with multiple sclerosis. Apart from recently described CD8+ tissue-resident...
In MS, an age-related decline in disease activity and a decreased efficacy of disease-modifying treatment have been linked to immunosenescence, state cellular dysfunction associated with chronic inflammation.To evaluate immunologic alterations we compared immune signatures peripheral blood (PB) CSF by flow cytometry patients relapsing-remitting (RR) (PB n = 38; 51) primary progressive (PP) MS 40; 36) respective controls 85).Analysis revealed significant changes cell composition, especially...
Abstract Several studies suggest a role for the peripheral immune system in pathophysiology of amyotrophic lateral sclerosis. However, comprehensive investigating intrathecal sclerosis are rare. To elucidate whether compartment-specific inflammation contributes to pathophysiology, we here investigated and profiles patients compared them with controls free neurological disorders (controls) dementia or primary progressive multiple Routine CSF parameters were examined 308 patients, including...
Abstract Background Primary central nervous system lymphoma (PCNSL) is a rare of the system, usually diffuse large B cell phenotype. Stereotactic biopsy followed by histopathology diagnostic standard. However, limited material available from CNS biopsies, thus impeding an in-depth characterization PCNSL. Methods We performed flow cytometry, single-cell RNA sequencing, and receptor sequencing PCNSL cells released material, blood, cerebrospinal fluid (CSF), spatial transcriptomics samples....
HIV-associated neurocognitive disorders (HAND) remain a challenge despite combination antiretroviral therapy (cART). Immune cell activation has been implicated to play major role in the development of HAND.In this study, we used multicolor flow cytometry on peripheral blood (PB) and cerebrospinal fluid (CSF) samples determine expression HLA-DR programmed death-1 (PD-1) CD4+ CD8+ T cells patients with chronic HIV infection. Expression levels were correlated HI virus load PB CSF,...
To report on a novel neuronal target antigen in 3 patients with autoimmune cerebellar degeneration.Three subacute to chronic ataxia and controls underwent detailed clinical neuropsychological assessment together quantitative high-resolution structural MRI. Sera CSF were subjected comprehensive autoantibody screening by indirect immunofluorescence assay (IFA) immunoblot. Immunoprecipitation lysates of hippocampus cerebellum combined mass spectrometric analysis was used identify the...
Distinct lesion topography in relapsing-remitting multiple sclerosis (RRMS) might be due to different antigen presentation and/or trafficking routes of immune cells into the central nervous system (CNS).To investigate whether distinct patterns (MS) associated with a predominance circulating T-helper cell subset as well their innate counterparts.Flow cytometric analysis lymphocytes derived from peripheral blood patients exclusively cerebral (n = 20) or predominantly spinal 12) disease...
To report 3 patients with relapsing-remitting multiple sclerosis (RRMS) showing vitiligo after treatment alemtuzumab.Retrospective case series including flow cytometric analyses and T-cell receptor (TCR) sequencing of peripheral blood mononuclear cells.We describe cases alemtuzumab-treated RRMS developing 52, 18, 14 months alemtuzumab initiation. Histopathology shows loss epidermal pigmentation absence melanocytes interface dermatitis CD8+ infiltration. Also compatible pathophysiologic...
Significance Multiple sclerosis is an autoimmune disease shaped by genetic and environmental factors. Because of the heterogeneity human population, it has been difficult to identify “immune signatures” disease. Here we investigated a cohort identical twin pairs who are discordant for multiple sclerosis. In each pair, immune signatures were remarkably similar, pointing strong influence shared However, when focused on subgroup seemingly healthy cotwins showed subtle signs “subclinical...
The cerebrospinal fluid (CSF) provides a unique glimpse into the central nervous system (CNS) compartment and offers insights immune processes associated with both healthy surveillance as well inflammatory disorders of CNS. latter include demyelinating disorders, such multiple sclerosis (MS) myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), that warrant different therapeutic approaches yet are not always straightforward to distinguish on clinical imaging grounds alone....
Autoimmune encephalitis (AIE) is a disabling inflammatory condition of the brain deemed to be due dysregulated immune response. Viral infections and malignancies together with certain genetic polymorphisms are thought contribute pathogenesis AIE, yet exact mechanisms remain insufficiently understood. Diagnosis AIE currently relies on clinical consensus criteria. However, diagnostic workup can challenging in some cases, potentially delaying treatment initiation associated poor outcomes. This...