IgG1 pan-neurofascin antibodies identify a severe yet treatable neuropathy with a high mortality
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.
Funding
GBS/CIDP Foundation International (Benson Fellowship, grant 1709HM001/SB17)
Medical Research Council (UK) (grant MR/P008399/1)
History
Comments
The original article is available at https://jnnp.bmj.com/Published Citation
Fehmi J. et al. IgG1 pan-neurofascin antibodies identify a severe yet treatable neuropathy with a high mortality. J Neurol Neurosurg Psychiatry. 2021;92(10):1089-1095Publication Date
16 August 2021External DOI
PubMed ID
34400540Department/Unit
- Beaumont Hospital
- School of Pharmacy and Biomolecular Sciences
Research Area
- Neurological and Psychiatric Disorders
Publisher
BMJVersion
- Published Version (Version of Record)