Anti‐neurofascin antibody in combined central and peripheral demyelination

Abstract

Neurofascin (NF), a cell adhesion molecule expressed in both the central nervous system (CNS) and the peripheral nervous system (PNS), plays important roles in developing and maintaining neural structures. There are several subtypes of NF resulting from post-translational modifications: NF155, 166, 180 and 186. Among them, NF155 and NF186 are expressed in the mature CNS/PNS. NF155 is present on the oligodendroglial cell surface in the CNS and on the Schwann cell surface in the PNS at paranodes, where it tightly connects with contactin and caspr on the axonal surface of the paranode, and acts as a stabilizer of the nodes of Ranvier. NF186 exists on the axonal surface at the nodes of Ranvier. NF186 is associated with voltage-gated Na channels (Nav), whereas both NF186 and Nav are anchored by ankyrin G. NF186 contributes to the clustering of Nav at the node. Combined central and peripheral demyelination (CCPD) is an inflammatory demyelinating disorder affecting both the CNS and PNS tissues. Distinct mechanisms including multiple sclerosis and chronic inflammatory demyelinating polyradiculoneuropathy have been hypothesized to play a role in this condition on the basis of distinctive clinical and laboratory findings. We detected anti-NF155 antibody by cell-based assay, enzyme-linked immunosorbent assay, and western blot in both the sera and cerebrospinal fluids of CCPD patients at high frequencies, but did not detect it in patients with other neurological disease or healthy controls. Herein, basic aspects and the clinical significance of NF as indispensable regulators and autoimmune target molecules are summarized. (Clin. Exp. Neuroimmunol.

Deletion of the Thrombin Proteolytic Site in Neurofascin 155 Causes Disruption of Nodal and Paranodal Organization

“…Autoantibodies to NF155 have been detected in various central and peripheral autoimmune demyelinating pathologies including Multiple Sclerosis (MS), Guillane-Barre syndrome (GBS), Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), and Combined Central and Peripheral Demyelination (CCPD) ( Mathey et al, 2007 ; Kawamura et al, 2013 ; Yamasaki, 2013 ; Cortese et al, 2016 ; Burnor et al, 2018 ; Doppler et al, 2018 ). In CIDP, the NF155 autoantibodies have been traced to a domain that includes the unique third FNIII-like domain in NF155 ( Ng et al, 2012 ).…”

Possible Combined Central and Peripheral Demyelination Presenting as Optic Neuritis, Cervical Myelitis, and Demyelinating Polyneuropathy with Marked Nerve Hypertrophy

“…There have been some cases of multiple sclerosis (MS) with peripheral neuropathy or chronic inflammatory demyelinating polyneuropathy (CIDP) with demyelinating plaques in the brain that are similar to those of MS ( 1 ). It has been hypothesized that these conditions represent a new disease entity called combined central and peripheral demyelination (CCPD) ( 2 - 5 ). With regard to the pathogenesis, various autoimmune mechanisms involving the common targeted neural antigens residing in both the peripheral and central nervous systems have been considered ( 6 ).…”