Autoimmune nodopathies: a clinical review

Autoimmune nodopathies are a subgroup of peripheral neuropathies characterized by autoantibodies targeting nodal and paranodal proteins such as neurofascin-155 (NF155), contactin-1 (CNTN1), and Contactin-associated protein 1 (Caspr1). Unlike chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), these conditions involve direct disruption of the node of Ranvier rather than demyelination, leading to their distinction from CIDP in the 2021 EAN/PNS guidelines. Paranodal autoantibodies are often of the IgG4 subclass, which does not activate complement. Pathogenicity is supported by correlation of antibody titers with clinical severity, evidence of axoglial detachment, disrupted axoglial binding, and passive transfer experiments. Patients present with severe distal-dominant sensorimotor neuropathy, sensory ataxia, tremor (especially in anti-NF155 cases), neuropathic pain, and occasionally membranous glomerulonephritis (anti-CNTN1 cases). Pan-neurofascin autoantibodies, directed against the nodal and paranodal isoform of neurofascin (NF186 and NF155) present with a very severe neuropathy typically requiring intensive care treatment. Autoimmune nodopathies account for 5-10% of the patients who fulfill diagnostic criteria of CIDP and can affect all ages, including children. Diagnosis relies on detecting specific autoantibodies via ELISA or cell-based assays and should be considered in patients with characteristic clinical and electrophysiological features. Standard CIDP treatments are typically ineffective, while plasma exchange and B cell-targeted therapies show good efficacy. Recognition of these distinct neuropathies is essential for appropriate diagnosis and management.