Neurofascin antibodies in chronic inflammatory demyelinating polyradiculoneuropathy: from intrinsic genetic background to clinical manifestations

There are bunch of autoantibodies, particularly autoantibodies against proteins located at the node of Ranvier, have been discovered and transformed the clinical management of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Neurofascin (NF) plays an important role in both the nodal and paranodal regions of the node of Ranvier. In this review, we focus on the two characteristic forms of neurofascin: NF186 and NF155, comparing the similarities and differences between them, reviewing the current knowledge on genetic backgrounds, pathogenesis, clinical manifestations, and management of patients with anti-neurofascin positive CIDP. Autoantibodies against neurofascin were mainly IgG4 isotype. Mutation of NFASC gene in human causes severe neurodevelopment disorders, and HLA DRB1*15 may be a strong risk factor for the development of anti-NF155 antibodies. Motor impairment, sensory ataxia, and tremor were the typical presentations of patients with anti-NF155+ CIDP, while tetraplegia and cranial nerve involvement were more common in patients with anti-NF186+ CIDP. Recent studies have depicted a relatively clear picture of anti-NF155+ CIDP, and the strong clinical correlation of NF186 with CIDP remains unclear. The genetic background of neurofascin will assist in future explorations.