The autoimmune vulnerability of the node of Ranvier

The nodes of Ranvier (NoR) are essential domains for nerve conduction and their disruption plays a key role in the pathophysiology of immune-mediated neuropathies. Our understanding of the specialized nodal regions and the immune mechanisms that affect them is growing and has led to the update of peripheral neuropathy classification to include the autoimmune nodopathies, defined by the site of the autoimmune attack. Autoantibodies directed against molecules of the nodal region (as neurofascin-140/186, neurofascin-155, contactin-1, contactin-associated protein 1, contactin-associated protein 2, gangliosides, LGI4, or myelin-associated glycoprotein), macrophage-induced paranodal demyelination, and phenotypic changes of the nodal domains of Schwann cells have been identified as key mechanisms in the pathogenesis of the autoimmune neuropathies. This review explores the current knowledge of the autoimmune vulnerability of the NoR, including the underlying mechanisms leading to dysfunction in the diverse autoimmune disorders.

Automated summary

The nodes of Ranvier (NoR) are crucial for nerve conduction and their disruption plays a significant role in immune-mediated neuropathies. Understanding the immune mechanisms affecting these specialized nodal regions has led to the classification of autoimmune nodopathies, which are defined by the site of autoimmune attack. Autoantibodies against molecules of the nodal region, paranodal demyelination induced by macrophages, and phenotypic changes of Schwann cells' nodal domains are identified as key mechanisms in the pathogenesis of autoimmune neuropathies. This review explores the autoimmune vulnerability of NoR and the underlying mechanisms leading to dysfunction in different autoimmune disorders.