Helena Radbruch

Helena Radbruch
Charité Universitätsmedizin Berlin | Charité · Institute of Neuropathology

About

157
Publications
25,643
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3,666
Citations
Citations since 2016
104 Research Items
2957 Citations
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Publications

Publications (157)
Article
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Background In severe cases, SARS-CoV-2 infection leads to acute respiratory distress syndrome (ARDS), often treated by extracorporeal membrane oxygenation (ECMO). During ECMO therapy, anticoagulation is crucial to prevent device-associated thrombosis and device failure, however, it is associated with bleeding complications. In COVID-19, additional...
Article
The factors influencing survival during severe infection are unclear. Extracellular chromatin drives pathology, but the mechanisms enabling its accumulation remain elusive. Here, we showed that in murine sepsis models, splenocyte death interfered with chromatin clearance through the release of the DNase I inhibitor actin. Actin inhibition was compe...
Article
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Circulating, blood-borne SARS-CoV-2-reactive memory T cells in persons so far unexposed to SARS-CoV-2 or the vaccines have been described in 20-100% of the adult population. They are credited with determining the efficacy of the immune response in COVID-19. Here, we demonstrate the presence of preexisting memory CD4+ T cells reacting to peptides of...
Article
Background Autopsies are a valuable tool for understanding disease, including COVID-19.Materials and methodsThe German Registry of COVID-19 Autopsies (DeRegCOVID), established in April 2020, serves as the electronic backbone of the National Autopsy Network (NATON), launched in early 2022 following DEFEAT PANDEMIcs.ResultsThe NATON consortium’s inte...
Article
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Background: Autopsy studies have provided valuable insights into the pathophysiology of COVID-19. Controversies remain about whether the clinical presentation is due to direct organ damage by SARS-CoV-2 or secondary effects, such as overshooting immune response. SARS-CoV-2 detection in tissues by RT-qPCR and immunohistochemistry (IHC) or electron...
Article
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Despite two years of intense global research activity, host genetic factors that predispose to a poorer prognosis of COVID-19 infection remain poorly understood. Here, we prioritise eight robust (e.g., ELF5) or suggestive but unreported (e.g., RAB2A) candidate protein mediators of COVID-19 outcomes by integrating results from the COVID-19 Host Gene...
Article
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The use of autopsies in medicine has been declining. The COVID-19 pandemic has documented and rejuvenated the importance of autopsies as a tool of modern medicine. In this review, we discuss the various autopsy techniques, the applicability of modern analytical methods to understand the pathophysiology of COVID-19, the major pathological organ find...
Article
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Background SARS-CoV-2 utilizes the ACE2 transmembrane peptidase as cellular entry receptor. However, whether SARS-CoV-2 in the alveolar compartment is strictly ACE2-dependent and to what extent virus-induced tissue damage and/or direct immune activation determines early pathogenesis is still elusive. Methods Spectral microscopy, single-cell/-nucle...
Article
Primary central nervous system post-transplant lymphoproliferative disorder (PCNS-PTLD) is strongly associated with Epstein-Barr virus (EBV). We analysed intrathecal production of EBV viral capsid antigen (VCA) immunoglobulin (Ig)G and IgA and Epstein-Barr nuclear antigen-1 (EBNA-1) IgG in nine patients with PNCS-PTLD and 20 patients with non-infla...
Article
Neurological symptoms in SARS-CoV-2-infected patients have been reported, but their cause remains unclear. In theory, the neurological symptoms observed after SARS-CoV-2 infection could be (1) directly caused by the virus infecting brain cells, (2) indirectly by our body's local or systemic immune response toward the virus, (3) by coincidental phen...
Article
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Primary lymphomas of the central nervous system (PCNSL) are mainly diffuse large B-cell lymphomas (DLBCLs) confined to the central nervous system (CNS). Molecular drivers of PCNSL have not been fully elucidated. Here, we profile and compare the whole-genome and transcriptome landscape of 51 CNS lymphomas (CNSL) to 39 follicular lymphoma and 36 DLBC...
Preprint
Patients with COVID-19 can have a variety of neurological symptoms, but the pathomechanism of CNS involvement in COVD-19 remains unclear. While routine cerebrospinal fluid (CSF) analyses in patients with neurological manifestations of COVID-19 generally show no or only mild inflammation, more detailed data on inflammatory mediators in the CSF of pa...
Preprint
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Post-acute lung sequelae of COVID-19 are challenging many survivors across the world, yet the mechanisms behind are poorly understood. Our results delineate an inflammatory cascade of events occurring along disease progression within fibrovascular niches. It is initiated by endothelial dysfunction, followed by heme scavenging of CD163+ macrophages...
Article
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Background Autopsies are an important tool in medicine, dissecting disease pathophysiology and causes of death. In COVID-19, autopsies revealed e.g., the effects on pulmonary (micro)vasculature or the nervous system, systemic viral spread, or the interplay with the immune system. To facilitate multicentre autopsy-based studies and provide a central...
Article
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Background: A fraction of patients with antibody-mediated autoimmune diseases remain unresponsive to first/second-line and sometimes even to escalation immunotherapies. Since these patients are still affected by poor outcome and increased mortality, we investigated the safety and efficacy of the plasma cell depleting anti-CD38 antibody daratumumab...
Preprint
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Hyperinflammation, coagulopathy and immune dysfunction are prominent in patients with severe infections. Extracellular chromatin clearance by plasma DNases suppresses such pathologies in mice but whether severe infection interferes with these pathways is unclear. Here, we show that patients with severe SARS-CoV-2 infection or microbial sepsis exhib...
Preprint
Full-text available
Despite two years of intense global research activity, host genetic factors that predispose to a poorer prognosis and severe course of COVID-19 infection remain poorly understood. Here, we identified eight candidate protein mediators of COVID-19 outcomes by establishing a shared genetic architecture at protein-coding loci using large-scale human ge...
Preprint
Background Autopsy studies have provided valuable insights into the pathophysiology of COVID-19. Controversies remain whether the clinical presentation is due to direct organ damage by SARS-CoV-2 or secondary effects, e.g. by an overshooting immune response. SARS-CoV-2 detection in tissues by RT-qPCR and immunohistochemistry (IHC) or electron micro...
Article
Full-text available
Background and Objectives To investigate whether the formation or retention of meningeal ectopic lymphoid tissue (mELT) can be inhibited by the sphingosine 1-phosphate receptor 1,5 modulator siponimod (BAF312) in a murine model of multiple sclerosis (MS). Methods A murine spontaneous chronic experimental autoimmune encephalomyelitis (EAE) model, f...
Article
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SARS-CoV-2 is a single-stranded RNA virus that causes coronavirus disease 2019 (COVID-19). Given its acute and often self-limiting course, components of the innate immune system are likely central in controlling virus replication thereby determining clinical outcome. Natural killer (NK) cells are innate lymphocytes with notable activity against a b...
Article
COVID-19-induced ‘acute respiratory distress syndrome’ (ARDS) is associated with prolonged respiratory failure and high mortality, but the mechanistic basis of lung injury remains incompletely understood. Here, we analyzed pulmonary immune responses and lung pathology in two cohorts of patients with COVID-19 ARDS using functional single cell genomi...
Article
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Background The detection of severe acute respiratory syndrome coronavirus (SARS-CoV-2) is challenging, particularly in post-mortem human tissues. However, there is increasing evidence for viral SARS-CoV-2 manifestation in non-respiratory tissues. In this context, it is a current matter of debate, whether SARS-CoV-2 shows hepatotropism. Case presen...
Preprint
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Primary lymphomas of the central nervous system (PCNSL) are mainly diffuse large B-cell lymphomas (DLBCLs) confined to the central nervous system (CNS). Despite extensive research, the molecular alterations leading to PCNSL have not been fully elucidated. In order to provide a comprehensive description of the genomic and transcriptional landscape o...
Article
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The SARS-CoV-2 pandemic has so far claimed over three and a half million lives worldwide. Though the SARS-CoV-2 mediated disease COVID-19 has first been characterized by an infection of the upper airways and the lung, recent evidence suggests a complex disease including gastrointestinal symptoms. Even if a direct viral tropism of intestinal cells h...
Article
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Objective To investigate whether anti-CD20 B-cell-depleting monoclonal antibodies (ɑCD20 mAbs) inhibit the formation or retention of meningeal ectopic lymphoid tissue (mELT) in a murine model of multiple sclerosis (MS). Methods We used a spontaneous chronic experimental autoimmune encephalomyelitis (EAE) model of mice with mutant T-cell and B-cell...
Article
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Viruses manipulate cellular metabolism and macromolecule recycling processes like autophagy. Dysregulated metabolism might lead to excessive inflammatory and autoimmune responses as observed in severe and long COVID-19 patients. Here we show that SARS-CoV-2 modulates cellular metabolism and reduces autophagy. Accordingly, compound-driven induction...
Article
Importance Myalgia, increased levels of creatine kinase, and persistent muscle weakness have been reported in patients with COVID-19. Objective To study skeletal muscle and myocardial inflammation in patients with COVID-19 who had died. Design, Setting, and Participants This case-control autopsy series was conducted in a university hospital as a...
Article
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Objectives Studies on the coronavirus disease 2019 (COVID-19) usually focus on middle aged and older adults. However, younger patients may present with severe COVID-19 and potentially fatal outcomes. For optimized, more specialized therapeutic regimens in this particular patient group, a better understanding of underlying pathomechanisms is of utte...
Article
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We aimed to evaluate SIGLEC1 (CD169) as a biomarker in multiple sclerosis (MS) and Neuromyelitis optica spectrum disorder (NMOSD) and to evaluate the presence of SIGLEC1 ⁺ myeloid cells in demyelinating diseases. We performed flow cytometry-based measurements of SIGLEC1 expression on monocytes in 86 MS patients, 41 NMOSD patients and 31 healthy con...
Article
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Lipid myopathies are rare and heterogeneous multi‐systemic diseases that may be hereditary or acquired and affect the skeletal muscle [1]. Four types usually demonstrate accumulation of lipids in muscle biopsy specimens that can be visualised using Oil‐Red‐O (ORO) stain. These comprise (i) Multiple Acyl‐CoA Dehydrogenase deficiency (MADD), (ii) Pri...
Article
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Objective: To assess the safety and efficacy of epigallocatechin-3-gallate (EGCG) add-on to glatiramer acetate (GA) in patients with relapsing-remitting multiple sclerosis (RRMS). Methods: We enrolled patients with RRMS (aged 18-60 years, Expanded Disability Status Scale [EDSS] score 0-6.5), receiving stable GA treatment in a multicenter, prospe...
Article
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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 the blood to study the dynamics of adaptive immune response in COVID-19 patients requiring intensive care. Before seroconversion in response to SARS-CoV-2 spike protein, peripheral plasmabl...
Article
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Calcium is a universal second messenger present in all eukaryotic cells. The mobilization and storage of Ca2+ ions drives a number of signaling-related processes, stress-responses or metabolic changes, all of which are relevant for the development of immune cells and their adaption to pathogens. Here, we introduce the FRET-reporter mouse YellowCaB...
Article
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Zusammenfassung Die gesundheitlichen Auswirkungen der Coronavirus-Krankheit 2019 (COVID-19) durch die Infektion von SARS-CoV‑2 (Schweres-Akutes-Respiratorisches–Syndrom-Coronavirus 2) werden mit der Ausbreitung der Pandemie immer deutlicher. Neben der Lunge sind auch andere Organe betroffen, welche die Morbidität und Mortalität deutlich beeinflusse...
Article
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Infection by the new corona virus strain SARS-CoV-2 and its related syndrome COVID-19 has been associated with more than two million deaths worldwide. Patients of higher age and with preexisting chronic health conditions are at an increased risk of fatal disease outcome. However, detailed information on causes of death and the contribution of pre-e...
Article
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Objectives In COVID-19, the adaptive immune response is of considerable importance and detailed cellular immune reactions in the hematological system of patients with severe SARS-CoV2-infection are yet to be clarified. Methods Here, we provide a morphologic characterization of both bone marrow (BM) and spleen (SPL) in 11 COVID-19 deceased with res...
Preprint
Full-text available
Objective We aimed to evaluate SIGLEC1 (CD169) as a biomarker in Multiple Sclerosis (MS) and Neuromyelitis optica spectrum disorder (NMOSD) and to evaluate the specificity of SIGLEC1 ⁺ myeloid cells for demyelinating diseases Methods We performed flow cytometry-based measurements of SIGLEC1 expression on monocytes in 86 MS patients, 41 NMOSD patie...
Article
Full-text available
The newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, a pandemic respiratory disease. Moreover, thromboembolic events throughout the body, including in the CNS, have been described. Given the neurological symptoms observed in a large majority of individuals with COVID-19, SARS-CoV-2 penetrance of the CNS...
Conference Paper
Introduction: By now, the pandemic spread of COVID-19 (coronavirus disease 2019) has claimed more than 600,000 lives. The adaptive immune response seems to play a major role in the progression of the disease, since entry of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is determined by a spike protein recognized by T helper cells. Th...
Preprint
Full-text available
Here we have analyzed the dynamics of the adaptive immune response triggered by SARS-CoV-2 in severely affected COVID-19 patients, as reflected by activated B cells egressing into the blood, at the single cell level. Early on, before seroconversion in response to SARS-CoV-2 spike protein, activated peripheral B cells displayed a type 1 interferon-i...
Preprint
Full-text available
The newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, a pandemic respiratory disease presenting with fever, cough, and often pneumonia. Moreover, thromboembolic events throughout the body including the central nervous system (CNS) have been described. Given first indication for viral RNA presence in the...
Article
Full-text available
The multiple sclerosis therapeutic teriflunomide is known to block the de novo synthesis of pyrimidine in mitochondria by inhibiting the enzyme dihydroorotate-dehydrogenase (DHODH). The metabolic processes of oxidative phosphorylation and glycolysis are further possible downstream targets. In healthy adult mice, high levels of dihydroorotate-dehydr...
Article
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Two‐photon microscopy (2PM) has brought unique insight into the mechanisms underlying immune system dynamics and function since it enables monitoring of cellular motility and communication in complex systems within their genuine environment—the living organism. However, use of 2PM in clinical settings is limited. In contrast, optical coherence tomo...
Preprint
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Development, function and maintenance of lymphocytes largely depend upon the cellular mobilization and storage of calcium ions. Within B lymphocytes, calcium can act as signal transducer, whilst at the same time it is crucial for maintaining the integrity of subcellular organelles. Due to the lack of absolute quantification methods, the amount of c...
Article
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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 patients with NMOSD and 17 patients with MS, as well as from 15 patients with Systemic Lupus Erythematosus (SLE) a...
Article
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In the past years, cellular metabolism of the immune system experienced a revival, as it has become clear that it is not merely responsible for the cellular energy supply, but also impacts on many signaling pathways and, thus, on diverse cellular functions. Label-free fluorescence lifetime imaging of the ubiquitous coenzymes NADH and NADPH (NAD(P)H...
Preprint
Full-text available
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 patients with NMOSD and 20 patients with MS, as well as from 18 patients with Systemic Lupus Erythematosus (SLE...
Article
Full-text available
Objective To investigate the relevance of dysfunctional T cells in immune-mediated myopathies. We analyzed T-cell exhaustion and senescence, in the context of programmed cell death protein 1 (PD1)-related immunity in skeletal muscle biopsies from patients with immune-mediated necrotizing myopathy (IMNM), sporadic inclusion body myositis (sIBM), and...
Article
Objectives: The aim of this study was to determine in vivo if brain inflammation leads to increased gadolinium (Gd) retention in brain tissue after repeated applications of Gd-based contrast agents (GBCAs). Materials and methods: Experimental autoimmune encephalomyelitis (EAE) was induced in female SJL/J mice (n = 6). Experimental autoimmune enc...
Article
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Background: Daclizumab is a monoclonal antibody that binds the high-affinity interleukin-2 receptor and was approved for the treatment of relapsing multiple sclerosis. Due to severe inflammatory brain disorders, the approval was suspended in March 2018. Objective and methods: This retrospective cohort study summarizes clinical, laboratory, radio...