Topic: autoantibodies

Autoantibodies against LGI1 cause limbic encephalitis with characteristic focal epileptic seizures and memory disorders. LGI1 is secreted by neurons and consists of two functional domains: a leucine-rich (LRR) and an epitempin (EPTP) region and forms complexes in synapses and axons via the receptors ADAM22/23 with Kv1 potassium channels and structural proteins such as PSD95 and glutamate receptors, whereby LGI1 can exert an influence on synaptic transmission and intrinsic excitability. To understand changes in neuronal function by LGI1 encephalitis, we used patients’ serum IgGs or monoclonal a

N-Methyl-D-Aspartate receptor (NMDAR) encephalitis is a neurological disorder mediated by autoantibodies targeting the NMDAR. Patients’ autoantibodies are pathogenic, as they cause neuronal dysfunction in vitro, and molecular and behavioral changes in mouse models of cerebroventricular transfer of patients’ antibodies. Active immunization models have confirmed these effects and informed on the development of adaptive immune responses. Here we aimed to characterize the accompanying innate immune response and how this contributes to disease pathogenesis. Female C57BL/6 mice were immunized with N

Anti-NMDA receptor (NMDAR) encephalitis is associated with the presence of autoantibodies against subunit 1 of the NMDA receptor (NR1) resulting in a variety of psychiatric symptoms as well as cognitive and motor impairments. These autoantibodies can arise in adulthood but also during pregnancy where they have been shown to affect the developing foetal brain and are implicated in neurodevelopmental disorders including autism and learning disabilities. Binding of these autoantibodies causes internalization of surface NMDAR leading to their reduced expression and disrupted signalling. To what ex

Glycine receptors (GlyRs) are crucial for the balance of excitation and inhibition in the mammalian spinal cord and brain stem. They belong to the superfamily of Cys-loop receptors and form pentameric ligand-gated chloride channels consisting of postsynaptic αβ heteromers or α homomers located extrasynaptically and at presynaptic membranes. Presynaptic GlyRs trigger depolarizing chloride currents upon activation by glycine spill-over.Autoantibodies (aAbs) against GlyRs are associated with the autoimmune disease Stiff Person Syndrome but also frequently found in patients with focal epilepsy. Lo

Autoantibodies (aAb) against N-methyl-D-aspartate receptor (NMDAR) mediate autoimmune Anti-NMDAR encephalitis. This leads to the development of various symptoms, including seizures, memory deficits, cognitive dysfunction, and psychosis. Our current understanding of the pathophysiology remains limited. Particularly the crucial molecular insights of autoantibody recognition and the influence of their binding on the function of NMDARs. To address these knowledge gaps, we characterized three patient-derived monoclonal antibodies in a multi-modal approach, encompassing super-resolution microscopy,