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Identification of new autoimmune encephalitis and characterization of antibody-mediated mechanisms
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[eng] Background: Autoimmune encephalitis is a new category of immune-mediated brain disorders characterized by the presence of antibodies targeting neurotransmitter receptors, ion channels, or neuronal cell-surface proteins. Most of these encephalitides were previously considered idiopathic, but systematic research in the last 16 years has led to the identification of new potentially pathogenic autoantibodies. Despite the advances in the field, there are still patients harboring uncharacterized antibodies with a clinical syndrome suggestive to be immune-mediated and a prominent or isolated cerebellar involvement. Recognition of these syndromes is critical, because patients can recover it they are treated promptly.
Among the recently identified syndromes, anti-IgLON5 disease stands out from the rest. Despite strong evidence pointing towards an autoimmune etiology (specific HLA association and in vitro effect of autoantibodies), neuropathological investigations reveal the presence of phosphorylated tau deposits, indicating a possible neurodegenerative mechanism. Whether the disease is has an autoimmune or neurodegenerative etiology is yet to be established.
Objectives: 1) To characterize the autoantibodies and define the clinical features of patients with antibody-mediated cerebellar ataxia; 2) To investigate the potential pathogenicity of these antibodies in hippocampal neurons and HEK293 cells expressing the target antigens; 3) To evaluate possible neurodegenerative events in hippocampal neurons after treatment with IgLON5 antibodies, and 4) To identify protein partners of IgLON5 and evaluate how autoantibodies can alter the interaction between them.
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LANDA MEDRANO, Jon. Identification of new autoimmune encephalitis and characterization of antibody-mediated mechanisms. [consulta: 15 de gener de 2026]. [Disponible a: https://hdl.handle.net/2445/217651]