Effects of IgLON5 antibodies on neuronal cytoskeleton: a link between autoimmunity and neurodegeneration.

Anti-IgLON5 disease is a neurological disorder characterized by autoantibodies against IgLON5 and pathological evidence of neuronal-specific tau accumulation. Here we report that patients' IgLON5 IgG, but not other cell-surface antibodies, disrupt the cytoskeletal organization in cultured rat hippocampal neurons resulting in dystrophic neurites and axonal swelling. Adsorption of IgLON5 IgG with HEK293 cells expressing IgLON5 abrogated the indicated cytoskeletal changes. These findings along an increase of levels of neurofilaments in patients' CSF suggest that IgLON5 IgG, unlike other cell-surface antibodies, disrupt neuronal cytoskeleton maintenance providing a link between autoimmunity and neurodegeneration. This article is protected by copyright. All rights reserved.