The immunology and neuropathology of the autoimmune nodopathies

The autoimmune nodopthies have recently emerged as a discrete subtype of inflammatory neuropathy. They are characterised by the presence of IgG class autoantibodies directed against structural components of the node of Ranvier, such as the axonal isoform of neurofascin (NF186), or flanking paranodes, where NF155, on the glial membrane, and the axonal complex of contactin-1 and contactin-associated protein-1 (Caspr1), are established targets. Although initially proposed to be atypical forms of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), many patients initially present with a clinical picture in keeping with the acute inflammatory neuropathy Guillain-Barré syndrome (GBS). Furthermore, compared to seronegative CIDP and GBS, the autoimmune nodopathies have distinct underlying immunological and neuropathogenic mechanisms. Crucially, the treatment response profile is also different, and patients often fail to respond to immunotherapies typically used in seronegative cases, such as immunoglobulin infusions and corticosteroids. However, responses to anti-CD20 B-cell depleting therapies are frequent and often long-lasting. This review provides on overview of the antigenic landscape of the node of Ranvier, and the broad concept of nodopathies, and summarises the immunology, neuropathology and clinical features of these disabling yet treatable disorders.