A5022938387- Autoimmune Neurological Disorders and Treatments
- Neuroscience and Neuropharmacology Research
- SARS-CoV-2 and COVID-19 Research
- RNA regulation and disease
- COVID-19 Clinical Research Studies
- Cellular transport and secretion
- Genetics and Neurodevelopmental Disorders
- Peripheral Neuropathies and Disorders
- Ion channel regulation and function
- Long-Term Effects of COVID-19
- Monoclonal and Polyclonal Antibodies Research
- Viral gastroenteritis research and epidemiology
- Respiratory viral infections research
- T-cell and B-cell Immunology
- Animal Virus Infections Studies
- Glycosylation and Glycoproteins Research
- Adenosine and Purinergic Signaling
- Neuroblastoma Research and Treatments
- Erythrocyte Function and Pathophysiology
- RNA and protein synthesis mechanisms
- SARS-CoV-2 detection and testing
- Cytomegalovirus and herpesvirus research
- Vagus Nerve Stimulation Research
- Glioma Diagnosis and Treatment
- Receptor Mechanisms and Signaling
Charité - Universitätsmedizin Berlin
2016-2025
German Center for Neurodegenerative Diseases
2016-2025
Humboldt-Universität zu Berlin
2019-2025
Freie Universität Berlin
2019-2025
Berlin Institute of Health at Charité - Universitätsmedizin Berlin
2021-2024
Brain Innovation (Netherlands)
2021
Ruhr University Bochum
2019
Neutralizing antibodies (nAbs) elicited against the receptor binding site (RBS) of spike protein wild-type severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are generally less effective recent variants concern. RBS residues Glu
The emergence of SARS-CoV-2 led to pandemic spread coronavirus disease 2019 (COVID-19), manifesting with respiratory symptoms and multi-organ dysfunction. Detailed characterization virus-neutralizing antibodies target epitopes is needed understand COVID-19 pathophysiology guide immunization strategies. Among 598 human monoclonal (mAbs) from 10 patients, we identified 40 strongly neutralizing mAbs. most potent mAb, CV07-209, neutralized authentic an IC50 value 3.1 ng/mL. Crystal structures...
See Zekeridou and Lennon (doi: 10.1093/aww213 ) for a scientific commentary on this article . Anti- N -methyl-D-aspartate receptor (NMDAR) encephalitis is recently discovered autoimmune syndrome associated with psychosis, dyskinesias, seizures. Little known about the cerebrospinal fluid autoantibody repertoire. Antibodies against NR1 subunit of NMDAR are thought to be pathogenic; however, direct proof lacking as previous experiments could not distinguish contribution further anti-neuronal...
COVID-19 intensive care patients can present with neurological syndromes, usually in the absence of SARS-CoV-2 cerebrospinal fluid (CSF). The recent finding some virus-neutralizing antibodies cross-reacting brain tissue suggests possible involvement specific autoimmunity.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Beta variant of concern (VOC) resists neutralization by major classes antibodies from COVID-19 patients and vaccinated individuals. In this study, serum Beta-infected revealed reduced cross-neutralization wild-type virus. From these patients, we isolated Beta-specific cross-reactive receptor-binding domain (RBD) antibodies. The Beta-specificity results recruitment VOC-specific clonotypes accommodation mutations present in Omicron...
Leucine-rich glioma-inactivated 1 (LGI1) encephalitis is the second most common antibody-mediated encephalopathy, but insight into intrathecal B-cell autoimmune response, including clonal relationships, isotype distribution, frequency, and pathogenic effects of single LGI1 antibodies, has remained limited.We cloned, expressed, tested antibodies from 90 antibody-secreting cells (ASCs) B cerebrospinal fluid (CSF) several patients with encephalitis.Eighty-four percent ASCs 21% memory encoded...
Abstract The protective efficacy of neutralizing antibodies (nAbs) elicited during natural infection with SARS-CoV-2 and by vaccination based on its spike protein has been compromised emergence the recent variants. Residues E484 K417 in receptor-binding site (RBS) are both mutated lineages first described South Africa (B.1.351) Brazil (B.1.1.28.1). nAbs isolated from patients preferentially encoded certain heavy-chain germline genes two most frequently antibody families (IGHV3-53/3-66...
Objective Maternal autoantibodies are a risk factor for impaired brain development in offspring. Antibodies (ABs) against the NR1 (GluN1) subunit of N ‐methyl‐ d ‐aspartate receptor (NMDAR) among most frequently diagnosed anti‐neuronal surface ABs, yet little is known about effects on fetal during pregnancy. Methods We established murine model utero exposure to human recombinant and isotype‐matched nonreactive control ABs. Pregnant C57BL/6J mice were intraperitoneally injected embryonic days...
Autoantibodies targeting the GABAA receptor (GABAAR) hallmark an autoimmune encephalitis presenting with frequent seizures and psychomotor abnormalities. Their pathogenic role is still not well-defined, given common overlap further autoantibodies lack of patient-derived mAbs. Five GABAAR mAbs from cerebrospinal fluid cells bound to various epitopes involving α1 γ2 subunits, variable binding strength partial competition. selectively reduced GABAergic currents in neuronal cultures without...
For coronavirus disease 2019 (COVID-19), effective and well-understood treatment options are still scarce. Since vaccine efficacy is challenged by novel variants, short-lasting immunity, hesitancy, understanding optimizing therapeutic remains essential. We aimed at better the effects of two standard-of-care drugs, dexamethasone anti-severe acute respiratory syndrome 2 (SARS-CoV-2) antibodies, on infection host responses. By using COVID-19 hamster models, pulmonary immune responses were...
Anti-NMDA receptor autoantibodies (NMDAR-Abs) in patients with NMDAR encephalitis cause severe disease symptoms resembling psychosis and cognitive dysfunction. After passive transfer of patients' cerebrospinal fluid or human monoclonal anti-GluN1-autoantibodies mice, we find a disrupted excitatory-inhibitory balance resulting from CA1 neuronal hypoexcitability, reduced AMPA (AMPAR) signaling, faster synaptic inhibition acute hippocampal slices. Functional alterations are also reflected...
Abstract Autoantibodies directed against the N-methyl-D-aspartate receptor (NMDAR-Ab) are pathogenic immunoglobulins detected in patients suffering from NMDAR encephalitis. NMDAR-Ab alter membrane trafficking, synaptic transmission and neuronal network properties, leading to neurological psychiatric symptoms patients. Patients often have very little damage but rapid massive (treatment-responsive) brain dysfunctions related an unknown early mechanism of NMDAR-Ab. Our understanding this...
Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most common autoimmune related to autoantibody-mediated synaptic dysfunction. Cerebrospinal fluid-derived human monoclonal NR1 autoantibodies showed low numbers of somatic hypermutations or were unmutated. These unexpected germline-configured antibodies weaker binding NMDAR than matured from same patient. In primary hippocampal neurons, germline strongly and specifically reduced total currents in a dose- time-dependent manner....
Abstract Psychiatric and neurological symptoms, as well cognitive deficits, represent a prominent phenotype associated with variable forms of autoimmune encephalitis, regardless the neurotransmitter receptor targeted by autoantibodies. The mechanistic underpinnings these shared major neuropsychiatric symptoms remain however unclear. Here, we investigate impacts patient-derived monoclonal autoantibodies against glutamatergic NMDAR (NMDAR mAb) inhibitory GABAaR (GABAaR signalling in...
Abstract Seizures are a prominent feature in N-Methyl-D-Aspartate receptor antibody (NMDAR antibody) encephalitis, distinct neuro-immunological disorder which specific human autoantibodies bind and crosslink the surface of NMDAR proteins thereby causing internalization state hypofunction. To further understand ictogenesis this disorder, to test potential treatment compound, we developed an mediated rat seizure model that displays spontaneous epileptiform activity vivo vitro. Using...
ABSTRACT Maternal anti-Caspr2 (Contactin-associated protein-like 2) antibodies have been associated with increased risk for autism spectrum disorder (ASD). Previous studies shown that in utero exposure to results a phenotype ASD-like features male mice. Here we ask whether four newly generated against Caspr2 are pathogenic the developing fetal brain and they function through similar means. Our show novel recognize different epitopes of Caspr2. In these elicits differential phenotypes...
Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a common autoimmune presenting with psychosis, dyskinesias, autonomic dysfunction and seizures. The underlying autoantibodies against the NR1 subunit are directly pathogenic by disrupting synaptic NMDAR currents. However, antibody titers correlate only partially clinical outcome, suggesting relevance of other factors such as affinity. We thus determined binding curves human monoclonal patients' cerebrospinal fluid (CSF)...
Anti-NMDA receptor (NMDAR) encephalitis is a severe neuropsychiatric disorder associated with autoantibodies against NMDARs, which cause variety of symptoms from prominent psychiatric and cognitive manifestations to seizures autonomic instability. Previous studies mainly focused on hippocampal effects these autoantibodies, helping explain mechanistic causes for impairment. However, antibodies' higher cortical network function, where they could contribute psychosis and/or seizures, have not...
The commensal microflora provides a repertoire of antigens that illicit mucosal antibodies. In some cases, these antibodies can cross-react with host proteins, inducing autoimmunity, or other microbial antigens. We demonstrate the oral microbiota induce salivary anti-SARS-CoV-2 Spike IgG via molecular mimicry. Anti-Spike in saliva correlated enhanced abundance Streptococcus salivarius 1 month after vaccination. Several human bacteria, including S. salivarius, were recognized by...
Anti-contactin associated protein receptor 2 (CASPR2) encephalitis is a severe autoimmune with variable clinical phenotype including behavioral abnormalities, cognitive decline, epileptic seizures, peripheral nerve hyperexcitability and neuropathic pain. The detailed mechanisms of how CASPR2 autoantibodies lead to synaptic dysfunction symptoms are largely unknown. Aiming for analyses from the molecular level, we isolated antibody-secreting cells cerebrospinal fluid two patients encephalitis....