A5014327058- Autophagy in Disease and Therapy
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Monoclonal and Polyclonal Antibodies Research
- Myasthenia Gravis and Thymoma
- Complement system in diseases
- Peripheral Neuropathies and Disorders
- Inflammatory Myopathies and Dermatomyositis
- Neuroinflammation and Neurodegeneration Mechanisms
- Immunotherapy and Immune Responses
- Parkinson's Disease and Spinal Disorders
- Glycosylation and Glycoproteins Research
- Antifungal resistance and susceptibility
- Platelet Disorders and Treatments
- Immune cells in cancer
- HIV Research and Treatment
- Viral-associated cancers and disorders
- Galectins and Cancer Biology
- Multiple Sclerosis Research Studies
- Systemic Lupus Erythematosus Research
- Phagocytosis and Immune Regulation
- Adenosine and Purinergic Signaling
- Inflammasome and immune disorders
- Toxoplasma gondii Research Studies
- Muscle Physiology and Disorders
University Hospital Münster
2019-2025
University Medical Center Freiburg
2025
Charité - Universitätsmedizin Berlin
2024
Humboldt State University
2024
Klinik und Poliklinik für Neurologie
2023
University of Zurich
1987-2021
University of Münster
2020-2021
University of Basel
2020
University of Bern
2020
Auckland University of Technology
2020
IgG molecules exert both pro- and antiinflammatory effector functions based on the composition of fragment crystallizable (Fc) domain glycan. Sialylated Fc domains have properties that are attributed to their ability increase activation threshold innate cells immune complexes by stimulating upregulation inhibitory Fcγ receptor IIB (FcγRIIB). Here, we report sialylation human monoclonal IgG1 impairs efficacy induce complement-mediated cytotoxicity (CDC). a CD20-targeting antibody had no...
Binding of the complement component C1q to CH2 domain antigen-bound IgG activates classical pathway and depends on its close proximity Fc fragments neighboring antibodies. subclasses contain a highly conserved asparagine 297 (N)-linked biantennary glycan within their domains which core structure can be extended with terminal galactose sialic acid residues. To investigate whether Fc-glycosylation regulates effector functions human subclasses, we cloned antigen binding region CD20-specific...
Myasthenia gravis (MG), Lambert-Eaton myasthenic syndrome (LEMS), and congenital syndromes (CMS) represent an etiologically heterogeneous group of (very) rare chronic diseases. MG LEMS have autoimmune-mediated etiology, while CMS are genetic disorders. A (strain dependent) muscle weakness due to neuromuscular transmission disorder is a common feature. Generalized requires increasingly differentiated therapeutic strategies that consider the enormous developments recent years. To include...
Primary progressive multiple sclerosis is a poorly understood disease entity with no specific prognostic biomarkers and scarce therapeutic options. We aimed to identify activity in by performing an RNA sequencing approach peripheral blood mononuclear cells from discovery cohort of 44 untreated patients belonging different clinical forms phases the disease, 12 healthy control subjects. A validation 58 26 subjects was included study replicate findings. The revealed interleukin 1 beta (IL1B)...
Macroautophagy, a homeostatic process that shuttles cytoplasmic constituents into endosomal and lysosomal compartments, has recently been shown to deliver antigens for presentation on major histocompatibility complex (MHC) class II molecules. Skeletal muscle fibers show high level of constitutive macroautophagy express MHC molecules upon immune activation. We found tumor necrosis factor-α (TNF-α), monokine overexpressed in inflammatory myopathies, led marked up-regulation skeletal myocytes....
Significance How autoreactive CD4 + T cells recognize their target antigen and induce sustained inflammation in organ-specific autoimmune diseases is incompletely understood. In an experimental model of multiple sclerosis, we show that accumulation myelin-specific within the CNS subsequent clinical disease development requires autophagy protein (ATG)-dependent phagocytosis dendritic (DCs). Absence ATG-dependent DCs abrogates myelin presentation to following oligodendroglial cells, its...
Whereas central nervous system (CNS) homeostasis is highly dependent on tissue surveillance by immune cells, dysregulated entry of leukocytes during autoimmune neuroinflammation causes severe immunopathology and neurological deficits. To invade the CNS parenchyma, encephalitogenic T helper (TH) cells must encounter their cognate antigen(s) presented local major histocompatibility complex (MHC) class II-expressing antigen-presenting (APCs). The precise mechanisms which CNS-associated APCs...
Myelin oligodendrocyte glycoprotein (MOG)-antibody (Ab)-associated diseases (MOGADs) account for a substantial proportion of pediatric and adult patients who present with acquired demyelinating disorders. Its pathogenesis optimal therapy are incompletely understood. We profiled systemic complement activation in MOGAD compared relapse-onset multiple sclerosis, neuromyelitis optica spectrum disorder, control healthy donors. Proteins indicative classical alternative were substantially increased...
Myelin oligodendrocyte glycoprotein (MOG)-antibody (Ab)-associated disease (MOGAD) is an inflammatory demyelinating of the CNS. Although MOG encephalitogenic in different mammalian species, mechanisms by which human MOG-specific Abs contribute to MOGAD are poorly understood. Here, we use a systems-level approach combined with high-dimensional characterization Ab-associated immune features deeply profile humoral responses 123 patients MOGAD. We show that age major determinant for...
CD4+Foxp3+ Treg cells are essential for maintaining self-tolerance and preventing excessive immune responses. In the context of Th1 responses, co-expression transcription factor T-bet with Foxp3 is to control T-bet-dependent expression CXCR3 directs site inflammation. However, suppressive mediators enabling effective responses at this unknown. study, we determined signature CXCR3+ arising in settings defined universal features using multiple Th1-dominated infection models. Our analysis a set...
Abstract Background and purpose Complement component 5 (C5) targeting therapies are clinically beneficial in patients with acetylcholine receptor antibody + (AChR‐Ab ) generalized myasthenia gravis (MG). That clearly implicates antibody‐mediated complement activation MG pathogenesis. Here, classical alternative pathways were profiled from different subgroups. Methods In a case–control study, concentrations of C3a, C5a sC5b9 simultaneously quantified, indicating general the system, whether...
Myasthenia gravis (MG) is an autoimmune disease most frequently caused by autoantibodies (auto-Abs) against the acetylcholine receptor (AChR) located at neuromuscular junction. Thymic follicular hyperplasia present in of patients with early-onset AChR-Ab+ MG (EOMG), but its cellular and molecular drivers development remain poorly understood. We constructed a single cell-based transcriptional profile lymphoid cell types thymi from 11 immunotherapy-naïve EOMG. Multiplex histology ELISA were...
HIV and EBV are human pathogens that cause a considerable burden to worldwide health. In combination, these viruses linked AIDS-associated lymphomas. We found EBV, which transforms B cells, renders them susceptible HIV-1 infection in CXCR4 CD4-dependent manner vitro CXCR4-tropic integrates into the genome of cells with same molecular profile as autologous CD4 + T cells. addition, we established humanized mouse model investigate vivo interactions upon coinfection. The respective mice...
Antibodies (Abs) specific for the low-density lipoprotein receptor-related protein 4 (LRP4) occur in up to 5% of patients with myasthenia gravis (MG). The objective this study was profile LRP4-Ab effector actions.
Biologics that target pathogenic antibodies (Abs) and their effector functions such as the complement inhibitor ravulizumab neonatal Fc receptor agonist efgartigimod have recently been approved for treatment of acetylcholine (AChR)-Ab-positive myasthenia gravis (MG), but comparative studies are lacking.
Invariant natural killer T (iNKT) cells are innate with powerful immune regulatory functions that recognize glycolipid antigens presented by the CD1D protein. While iNKT cell-activating glycolipids currently being explored for their efficacy to improve immunotherapy against infectious diseases and cancer, little is known about mechanisms control antigen presentation cell activation in vivo. molecules survey endocytic pathways bind lipid MHC class II-containing compartments (MIICs) before...
Abstract Intravenous immunoglobulin (IVIG) are purified IgG preparations made from the pooled plasma thousands of healthy donors and being tested in preclinical mouse models. Inherent challenges, however, pluripotency IVIG its xenogeneicity animals. can alter viability human neutrophils via agonistic antibodies to Fas Siglec-9. In this study, we compared effects on using different death assays. Different commercial similarly induced cytokine-dependent neutrophils, whereas they had no...
Chronic inflammatory demyelinating polyneuropathy (CIDP) is the most common chronic autoimmune neuropathy. While both cell-mediated and humoral mechanisms contribute to its pathogenesis, rapid clinical response plasmapheresis implicates a circulating factor responsible for peripheral nerve injury. We report that treatment-naïve patients with CIDP show increased serum CSF levels of anaphylatoxin C5a soluble terminal complement complex (sTCC). Systemic activation correlates disease severity as...
Abstract Foxp3 + regulatory T (Treg) cells are essential for maintaining peripheral tolerance and preventing autoimmunity. While genetic factors may predispose autoimmunity, additional environmental triggers, such as viral infections, usually required to initiate the onset of disease. Here, we show that infection with LCMV results in type I IFN-dependent Treg cell loss is rapidly compensated by conversion expansion Vβ5 conventional into iTreg cells. Using Vβ5-deficient mice, these...