RT Journal Article SR Electronic T1 IgG1 pan-neurofascin antibodies identify a severe yet treatable neuropathy with a high mortality JF Journal of Neurology, Neurosurgery & Psychiatry JO J Neurol Neurosurg Psychiatry FD BMJ Publishing Group Ltd SP 1089 OP 1095 DO 10.1136/jnnp-2021-326343 VO 92 IS 10 A1 Janev Fehmi A1 Alexander J Davies A1 Jon Walters A1 Timothy Lavin A1 Ryan Keh A1 Alexander M Rossor A1 Tudor Munteanu A1 Norman Delanty A1 Rhys Roberts A1 Dirk Bäumer A1 Graham Lennox A1 Simon Rinaldi YR 2021 UL http://jnnp.bmj.com/content/92/10/1089.abstract AB 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.