A5084248314- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Systemic Lupus Erythematosus Research
- Monoclonal and Polyclonal Antibodies Research
- Calcium signaling and nucleotide metabolism
- Multiple Sclerosis Research Studies
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- SARS-CoV-2 and COVID-19 Research
- CAR-T cell therapy research
- Chronic Lymphocytic Leukemia Research
- Peripheral Neuropathies and Disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- COVID-19 Clinical Research Studies
- Cancer Immunotherapy and Biomarkers
- Immune responses and vaccinations
- Cell Adhesion Molecules Research
- Virus-based gene therapy research
- Immunodeficiency and Autoimmune Disorders
- CRISPR and Genetic Engineering
- Galectins and Cancer Biology
- Autoimmune Neurological Disorders and Treatments
- Viral Infectious Diseases and Gene Expression in Insects
- Vasculitis and related conditions
- Multiple Myeloma Research and Treatments
- Atherosclerosis and Cardiovascular Diseases
Charité - Universitätsmedizin Berlin
2018-2025
German Rheumatism Research Centre
2017-2025
Humboldt-Universität zu Berlin
2018-2025
Freie Universität Berlin
2018-2025
Berlin Institute of Health at Charité - Universitätsmedizin Berlin
2018-2025
Leibniz Association
2020-2025
Friedrich-Alexander-Universität Erlangen-Nürnberg
2024
Universitätsklinikum Erlangen
2024
Daratumumab, a human monoclonal antibody that targets CD38, depletes plasma cells and is approved for the treatment of multiple myeloma. Long-lived are implicated in pathogenesis systemic lupus erythematosus because they secrete autoantibodies, but unresponsive to standard immunosuppression. We describe use daratumumab induced substantial clinical responses two patients with life-threatening lupus, sustained by maintenance therapy belimumab, an B-cell activating factor. Significant depletion...
The pathogenesis of severe COVID-19 reflects an inefficient immune reaction to SARS-CoV-2. Here we analyze, at the single cell level, plasmablasts egressed into blood study dynamics adaptive response in patients requiring intensive care. Before seroconversion SARS-CoV-2 spike protein, peripheral display a type 1 interferon-induced gene expression signature; however, following seroconversion, lose this signature, express instead signatures induced by IL-21 and TGF-β, produce mostly IgG1 IgA1....
Chimeric antigen receptor (CAR) redirected T cells are potent therapeutic options against hematological malignancies. The current dominant manufacturing approach for CAR depends on retroviral transduction. With the advent of gene editing, insertion a CD19-CAR into cell (TCR) alpha constant (TRAC) locus using adeno-associated viruses transfer was demonstrated, and these showed improved functionality over their retrovirally transduced counterparts. However, clinical-grade production is complex...
Abstract Background and purpose A fraction of patients with antibody‐mediated autoimmune diseases remain unresponsive to first‐/second‐line sometimes even escalation immunotherapies. Because these are still affected by poor outcome increased mortality, we investigated the safety efficacy plasma cell‐depleting anti‐CD38 antibody daratumumab in life‐threatening, diseases. Methods In this retrospective, single‐center case series, seven autoantibody‐driven neurological (autoimmune encephalitis,...
Objective Treatment-refractory antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a life-threatening condition without evidence-based treatment options. One emerging option for several antibody-mediated autoimmune diseases the anti-CD38 daratumumab, which depletes autoantibody-secreting plasma cells. Methods We treated two patients with severe AAV renal and pulmonary manifestation despite induction therapy rituximab cyclophosphamide four to eight doses of 1800 mg...
Abstract Diverse autoantibodies were suggested to contribute severe outcomes of COVID‐19, but their functional implications are largely unclear. ACE2, the SARS‐CoV‐2 receptor and a key regulator blood pressure, was described be one many targets in COVID‐19. ACE2 its soluble form (sACE2) is highly elevated critically ill patients, raising question whether sACE2:spike complexes induce reactivity. Screening 247 COVID‐19 we observed sACE2 anti‐ACE2 IgG that poorly correlated. Interestingly,...
Given its uniformly high expression on plasma cells, CD38 has been considered as a therapeutic target in patients with systemic lupus erythematosus (SLE). Herein, we investigate the distribution of by peripheral blood leukocyte lineages to evaluate potential effect CD38-targeting antibodies these immune cell subsets and delineate use biomarker SLE. We analyzed flow mass cytometry two different cohorts, comprising total 56 SLE patients. The levels were subsequently correlated across subsets,...
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...
Time-correlated single-photon counting combined with multi-photon laser scanning microscopy has proven to be a versatile tool perform fluorescence lifetime imaging in biological samples and, thus, shed light on cellular functions, both vitro and vivo. Here, by means of phasor-analyzed endogenous NAD(P)H (nicotinamide adenine dinucleotide (phosphate)) imaging, we visualize the shift metabolism healthy human neutrophil granulocytes during phagocytosis Staphylococcus aureus pHrodo™ beads. We...
Objective: To investigate whether low-density granulocytes (LDGs) are an immunophenotypic feature of patients with multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD). Methods: Blood samples were collected from 20 NMOSD and 17 MS, as well 15 Systemic Lupus Erythematosus (SLE) 23 Healthy Donors (HD). We isolated peripheral blood mononuclear cells (PBMCs) density gradient separation stained the antibodies against CD14, CD15, CD16, CD45, analyzed by flow cytometry imaging...
Abstract We aimed to evaluate SIGLEC1 (CD169) as a biomarker in multiple sclerosis (MS) and Neuromyelitis optica spectrum disorder (NMOSD) the presence of + myeloid cells demyelinating diseases. performed flow cytometry-based measurements expression on monocytes 86 MS patients, 41 NMOSD patients 31 healthy controls. Additionally, we histologically evaluated acute chronic brain lesions well other neurological found elevated 16/86 (18.6%) 4/41 (9.8%) patients. Almost all with high levels...
Granulomatosis with Polyangiitis (GPA) is a small vessel vasculitis typically associated release of neutrophil extracellular traps (NETs) by activated neutrophils. In this study, we further aimed to investigate the contributions neutrophils and NETs complex disease pathogenesis. We characterized phenotype their capacity induce NETs. addition, level circulating NETs, determined elastase/DNA complexes, patient sera degrade were investigated from blood samples 12 GPA patients, 21 patients...
Baló's concentric sclerosis (BCS) is a rare condition characterized by concentrically layered white matter lesions. While its pathogenesis unknown, hypoxia-induced tissue injury and chemotactic stimuli have been proposed as potential causes of BCS lesion formation. has suggested to be variant multiple (MS). Here, we aimed elucidate similarities differences between MS describing morphology localization in high-resolution 7 Tesla (7 T) magnetic resonance imaging (MRI) scans.Ten patients with...
In aging individuals, both protective as well regulatory immune functions are declining, resulting in an increased susceptibility to infections autoimmunity. NADPH oxidase 2-deficiency cell subsets has been shown be associated with aging. Using intravital marker-free NAD(P)H fluorescence lifetime imaging, we have previously identified microglia/myeloid cells and astrocytes main cellular sources of oxidases (NOX) activity the CNS during neuroinflammation, due over-activation NOX). The...
<h3>Background:</h3> Autoantibody production by long-lived plasma cells (PCs) have been implicated in the pathogenesis of systemic lupus erythematosus (SLE) but targeting them remains a therapeutic challenge. <h3>Objectives:</h3> We aimed to investigate safety and efficacy anti-CD38 monoclonal antibody daratumumab moderate severe SLE. This reagent depletes PCs is approved for treatment multiple myeloma. <h3>Methods:</h3> A single-center, phase 2, open-label investigator-initiated study was...
Abstract Objectives To evaluate and compare the diagnostic accuracy of SIGLEC1, a surrogate marker type I IFN, with established biomarkers in an inception cohort systemic lupus erythematosus (SLE). Methods SIGLEC1 was analysed by flow cytometry 232 patients referred to our institution suspected SLE between October 2015 September 2020. Results confirmed 76 (32.8 %) according 2019 EULAR/ACR classification criteria their values were significantly higher compared without (P &lt;0.0001). A...
Abstract Here we have analyzed the dynamics of adaptive immune response triggered by SARS-CoV-2 in severely affected COVID-19 patients, as reflected activated B cells egressing into blood, at single cell level. Early on, before seroconversion to spike protein, peripheral displayed a type 1 interferon-induced gene expression signature. After seroconversion, lost this signature, expressed IL-21- and TGF-β-induced signatures, mostly IgG1 IgA1. In sustained reaction until day 59, shifted IgA2,...
<h3>Background</h3> Given their contribution to the chronicity of autoimmune response, long-lived plasma cells (PCs) resemble an attractive treatment target in systemic lupus erythematosus (SLE) and other autoantibody-mediated diseases. We have recently reported successful daratumumab, a CD38-targeting human monoclonal antibody, two refractory patients with SLE [1], demonstrating clinically relevant depletion marked reduction anti-double-stranded DNA (dsDNA) antibodies clinical improvement...
Chimeric Antigen Receptor (CAR) redirected T cells are a potent treatment option for certain hematological malignancies. Recently, site-specific insertion of CARs into the cell receptor (TCR) alpha constant (TRAC) locus using gene editing and adeno-associated viruses was shown to generate CAR with improved functionality over their retrovirally transduced counterparts. However, development transfer is complex associated extensive costs at clinical stages. Here, we provide an economical...
Abstract Objective To investigate whether low-density granulocytes (LDGs) are a immunophenotypic feature of patients with multiple sclerosis (MS) and/or neuromyelitis optica spectrum disorder (NMOSD). Methods Blood samples were collected from 26 NMOSD and 20 MS, as well 18 Systemic Lupus Erythematosus (SLE) 23 Healthy Donors (HD). We isolated peripheral blood mononuclear cells (PBMCs) density gradient separation stained the antibodies against CD14, CD15, CD16, CD45, analysed by flow...
ZUSAMMENFASSUNG CD38 ist ein Typ-II-Glykoprotein und Ektoenzym, das auf kurz- langlebigen Plasmazellen stark exprimiert wird, während es anderen lymphoiden Zellen, myeloischen Zellen nicht hämatopoetischen nur schwach wird. Dieses Expressionsmuster macht zu einem interessanten Ziel für einen Plasmazell-gerichteten Therapieansatz bei Multiplem Myelom bereits als Therapieoption fest verankert. Bei Autoantikörper-vermittelten Autoimmunerkrankungen zielt dieser Ansatz eine Depletion von...