TY - JOUR T1 - IgG<sub>1</sub> pan-neurofascin antibodies identify a severe yet treatable neuropathy with a high mortality JF - Journal of Neurology, Neurosurgery &amp; Psychiatry JO - J Neurol Neurosurg Psychiatry SP - 1089 LP - 1095 DO - 10.1136/jnnp-2021-326343 VL - 92 IS - 10 AU - Janev Fehmi AU - Alexander J Davies AU - Jon Walters AU - Timothy Lavin AU - Ryan Keh AU - Alexander M Rossor AU - Tudor Munteanu AU - Norman Delanty AU - Rhys Roberts AU - Dirk Bäumer AU - Graham Lennox AU - Simon Rinaldi Y1 - 2021/10/01 UR - http://jnnp.bmj.com/content/92/10/1089.abstract N2 - Objectives We aimed to define the clinical and serological characteristics of pan-neurofascin antibody-positive patients.Methods We tested serum from patients with suspected immune-mediated neuropathies for antibodies directed against nodal/paranodal protein antigens using a live cell-based assay and solid-phase platform. The clinical and serological characteristics of antibody-positive and seronegative patients were then compared. Sera positive for pan-neurofascin were also tested against live myelinated human stem cell-derived sensory neurons for antibody binding.Results Eight patients with IgG1-subclass antibodies directed against both isoforms of the nodal/paranodal cell adhesion molecule neurofascin were identified. All developed rapidly progressive tetraplegia. Cranial nerve deficits (100% vs 26%), autonomic dysfunction (75% vs 13%) and respiratory involvement (88% vs 14%) were more common than in seronegative patients. Four patients died despite treatment with one or more modalities of standard immunotherapy (intravenous immunoglobulin, steroids and/or plasmapheresis), whereas the four patients who later went on to receive the B cell-depleting therapy rituximab then began to show progressive functional improvements within weeks, became seronegative and ultimately became functionally independent.Conclusions IgG1 pan-neurofascin antibodies define a very severe autoimmune neuropathy. We urgently recommend trials of targeted immunotherapy for this serologically classified patient group.Data are available upon reasonable request. The data that support the findings of this study are available from the corresponding author, upon reasonable request. ER -