Neurofascin-155 as a putative antigen in combined central and peripheral demyelination

Combined central and peripheral demyelination (CCPD) encompasses a wide array of disorders ranging from myeloradiculoneuritis and encephalomyeloradiculoneuritis, which often occur after infection or vaccination, to co-occurrence of multiple sclerosis (MS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Antibodies directed to neurofascin-155 (NF155), a protein expressed in both CNS and peripheral nervous system myelin and involved in axo-glial coupling at the paranodal regions that flank the node of Ranvier, have been identified with high frequency in Japanese patients with CCPD. However, these data await independent confirmation in different case series. Moreover, antibodies to NF155 have been reported consistently, although with low frequency, in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), thus questioning their specificity and pathogenicity in CCDP. Finally, there is no current consensus on the gold standard technique for anti-NF155 antibody testing, and previous studies used rat or human NF155-based ELISA, cell-based assay (CBA), and immunohistochemistry (IHC) on mouse teased fibers. The aims of this study were to confirm the association between anti-NF155 antibodies and CCPD in a Caucasian population and to assess the diagnostic accuracy of the currently available techniques for anti-NF155 antibody testing.