A5045601856- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Multiple Sclerosis Research Studies
- Monoclonal and Polyclonal Antibodies Research
- Peripheral Neuropathies and Disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- CAR-T cell therapy research
- Multiple Myeloma Research and Treatments
- Autoimmune Neurological Disorders and Treatments
- Immunodeficiency and Autoimmune Disorders
- Inflammatory Myopathies and Dermatomyositis
- Cytokine Signaling Pathways and Interactions
- Neuroscience and Neuropharmacology Research
- Immune Response and Inflammation
- Protein Structure and Dynamics
- Diabetes and associated disorders
- Systemic Lupus Erythematosus Research
- Lipid Membrane Structure and Behavior
- Hair Growth and Disorders
- Dermatology and Skin Diseases
- Hematopoietic Stem Cell Transplantation
- Hereditary Neurological Disorders
- Adenosine and Purinergic Signaling
- Bacterial Genetics and Biotechnology
Ludwig-Maximilians-Universität München
2015-2024
Munich Cluster for Systems Neurology
2014-2024
Max Planck Institute of Neurobiology
2007-2024
LMU Klinikum
2014-2024
Institute of Neuroimmunology of the Slovak Academy of Sciences
2019-2022
University Medical Center Hamburg-Eppendorf
2016
Max Planck Institute of Biochemistry
1997-2016
Universität Hamburg
2016
University of Oxford
2016
John Radcliffe Hospital
2016
Abstract A recombinant protein corresponding to the Ig-like domain of myelin oligodendrocyte glycoprotein (MOG) and synthetic 15-mer peptides whole MOG molecule with eight amino acid overlaps were screened for their ability induce experimental allergic encephalomyelitis (EAE) in Biozzi AB/H (H-2dq1) SJL (H-2S) mice. Clinical histologic evidence EAE developed after sensitization both In mice at least three epitopes within residues 1-22, 43-57, 134-148 induced clinical EAE, whereas only...
Psoriasis vulgaris is a common T cell–mediated inflammatory skin disease with suspected autoimmune pathogenesis. The human leukocyte antigen (HLA) class I allele, HLA-C*06:02, the main psoriasis risk gene. Epidermal CD8+ cells are essential for development. Functional implications of HLA-C*06:02 and mechanisms lesional cell activation in psoriasis, however, remained elusive. Here we identify melanocytes as skin-specific target an HLA-C*06:02–restricted psoriatic response. We found that...
To study the longitudinal dynamics of anti-myelin oligodendrocyte glycoprotein (MOG) autoantibodies in childhood demyelinating diseases.We addressed kinetics anti-MOG immunoglobulins a prospective comprising 77 pediatric patients. This was supplemented by cross-sectional analyzing 126 patients with acute demyelination and 62 adult multiple sclerosis (MS). MOG-transfected cells were used for detection antibodies flow cytometry.Twenty-five children who immunoglobulin (Ig) positive at disease...
We asked whether autoantibodies against neurofascin (NF)186 or NF155, both localized at the nodes of Ranvier, are present in serum patients with inflammatory neuropathy, and NF-specific monoclonal antibodies pathogenic vivo.We cloned human NF155 NF186, developed an ELISA cell-based assay to screen for NF a total 434 donors including 294 Guillain-Barré syndrome variants acute demyelinating polyneuropathy (AIDP), motor axonal chronic (CIDP). characterized reactive samples by isotyping, tissue...
Significance Oligoclonal bands (OCBs) of the cerebrospinal fluid (CSF) are a hallmark multiple sclerosis (MS). They expanded antibody species that detectable in >95% patients. Because several OCB and polyclonal antibodies present CSF sample, it was for technical reasons thus far not possible to isolate distinct OCBs identify their antigens. Here we combined refined biochemical analysis, proteomics, transcriptomics molecularly characterize antibodies. We produced six recombinant...
Objective Autoantibodies against myelin oligodendrocyte glycoprotein (MOG) occur in a proportion of patients with inflammatory demyelinating diseases the central nervous system (CNS). We analyzed their pathogenic activity by affinity‐purifying these antibodies (Abs) from and transferring them to experimental animals. Methods Patients Abs MOG were identified cell‐based assay. determined cross‐reactivity rodent recognized epitopes. produced correctly folded extracellular domain...
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,...
Atherosclerotic plaques form in the inner layer of arteries triggering heart attacks and strokes. Although T cells have been detected atherosclerosis, tolerance dysfunction as a disease driver remains unexplored. Here we examine checkpoints atherosclerotic plaques, artery tertiary lymphoid organs lymph nodes mice burdened by advanced via single-cell RNA sequencing paired with cell antigen receptor sequencing. Complex patterns deteriorating peripheral were observed being most pronounced...
We surveyed the T cell receptor repertoire in three separate compartments (brain, cerebrospinal fluid, and blood) of two multiple sclerosis patients who initially had diagnostic brain biopsies to clarify their unusual clinical presentation but were subsequently confirmed have typical sclerosis. One biopsy specimens been previously investigated by microdissection single-cell PCR determine clonal composition brain-infiltrating cells at level. Using complementarity-determining region 3...
Multiple sclerosis (MS) is an inflammatory demyelinating disease where T cells attack the brain and spinal cord. It known that often particular T-cell clones are expanded in target tissue, but it still unknown, whether identical present at distinct anatomical sites, or spectrum locally diverse. Therefore we compared receptor (TCR) repertoire lesions normal-appearing white matter (NAWM) from post-mortem brains of four MS patients. We analysed 19 (inactive demyelinated, 15; slowly expanding...
Antibodies against myelin oligodendrocyte glycoprotein (MOG) have been identified in a subgroup of pediatric patients with inflammatory demyelinating disease the central nervous system (CNS) and some neuromyelitis optica spectrum disorder (NMOSD). The aim this study was to examine frequency, clinical features, long-term course anti-MOG antibodies European cohort NMO/NMOSD.Sera from 48 NMO/NMOSD relapsing-remitting multiple sclerosis (RR-MS) were tested for anti-aquaporin-4 (AQP4) cell-based...
Rasmussen encephalitis (RE) is a rare neurological disorder of childhood characterized by uni-hemispheric inflammation, progressive deficits and intractable focal epilepsy. Destruction neurons astrocytes cytotoxic CD8 T cells has been proposed as pathogenic mechanism underlying this enigmatic disorder. We tested hypothesis analysing the clonal composition T-cell receptor (TCR) repertoire CD4+ CD8+ using complementarity determining region 3 (CDR3) spectratyping from peripheral blood...
Abstract Autoantibodies targeting conformationally intact myelin oligodendrocyte glycoprotein (MOG) are found in different inflammatory diseases of the CNS, but their antigenic epitopes have not been mapped. We expressed mutants MOG on human HeLa cells and analyzed sera from 111 patients (104 children, 7 adults) who recognized cell-bound MOG, had diseases, including acute disseminated encephalomyelitis (ADEM), one episode transverse myelitis or optic neuritis, multiple sclerosis (MS),...
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...
We investigated a patient who developed multiple sclerosis (MS) during treatment with the CTLA4-blocking antibody ipilimumab for metastatic melanoma. Initially he showed subclinical magnetic resonance imaging (MRI) changes (radiologically isolated syndrome). Two courses of were each followed by clinical episode MS, 1 which was accompanied massive increase MRI activity. Brain biopsy confirmed active, T-cell type MS. Quantitative next generation sequencing receptor genes revealed distinct...
Multiple sclerosis (MS) is a disabling disease of the CNS. Inflammatory features MS include lymphocyte accumulations in CNS and cerebrospinal fluid (CSF). The preclinical events leading to established are still enigmatic. Here we compared gene expression patterns CSF cells from MS-discordant monozygotic twin pairs. Six "healthy" co-twins, who carry maximal familial risk for developing MS, showed subclinical neuroinflammation (SCNI) with small MRI lesions. Four these subjects had oligoclonal...
Abstract Rasmussen encephalitis (RE) is a rare paediatric epilepsy with uni-hemispheric inflammation and progressive neurological deficits. To elucidate RE immunopathology, we applied T-cell receptor (TCR) sequencing to blood ( n =23), cerebrospinal fluid =2) brain biopsies =5) of patients, controls. patients present peripheral CD8 + expansion its strength correlates disease severity. In addition, the only prominent expansions in CNS. Consistently, common clones are shared between who also...
In polymyositis (PM), CD8+ T cell receptor (TCR) alpha/beta + cells invade and destroy major histocompatibility complex class I-positive muscle fibers. We combined polymerase chain reaction (PCR) double-fluorescence immunocytochemistry to analyze the repertoire expressed in of PM patients. patient 1, inverse PCR revealed a preferential usage TCR V alpha 33.1, beta 13.1, 5.1. Six six 33.1+ clones five seven 13.1+ had identical nucleotide sequences. contrast, 5.1+ TCRs were more heterogeneous....