Journal article
IgG1 pan-neurofascin antibodies identify a severe yet treatable neuropathy with a high mortality
- Abstract:
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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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, 23.3MB, Terms of use)
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- Publisher copy:
- 10.1136/jnnp-2021-326343
Authors
- Publisher:
- BMJ Publishing Group
- Journal:
- Journal of Neurology, Neurosurgery and Psychiatry More from this journal
- Volume:
- 92
- Issue:
- 10
- Pages:
- 1089-1095
- Place of publication:
- England
- Publication date:
- 2021-08-16
- Acceptance date:
- 2021-08-09
- DOI:
- EISSN:
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1468-330X
- ISSN:
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0022-3050
- Pmid:
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34400540
- Language:
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English
- Keywords:
- Pubs id:
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1192233
- Local pid:
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pubs:1192233
- Deposit date:
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2021-09-08
Terms of use
- Copyright holder:
- Fehmi et al
- Copyright date:
- 2021
- Rights statement:
- © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.
- Licence:
- CC Attribution (CC BY)
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