Science News: IgG1 Pan-Neurofascin Antibodies Identify a Severe Yet Treatable Neuropathy With a High Mortality

Published February 20, 2022

Education Science News

Submitted by: Pritikanta Paul, MD
Edited by: Francisco Gomez, MD

Fehmi J, Davies AJ, Walters J, et al. IgG1 pan-neurofascin antibodies identify a severe yet treatable neuropathy with a high mortality. J Neurol Neurosurg Psychiatry. 2021 Oct;92(10):1089-1095. doi: 10.1136/jnnp-2021-326343

Summary: Patients with autoantibodies against nodal/paranodal proteins present with a distinct clinical phenotype. Autoantibodies are mostly of the non-complement fixing IgG4 subtype and have been linked to Guillain-Barré syndrome (GBS) type presentation.
The authors in this study tested patients with suspected inflammatory neuropathies for IgG antibodies against nodal (NF186) and paranodal (NF155, CNTN1 and Caspr1) cell adhesion molecules using a live, cell-based assay (CBA) and found eight patients (1.2%) with IgG1 antibodies to both NF186/NF140 isoforms and NF155 isoforms, but no IgG3 or IgG4 subclass antibodies. Clinical and laboratory and histopathological features were assessed and compared with seronegative and patients with other nodal/paranodal antibodies.
Pan-neurofascin antibody-positive patients exhibited a severe phenotype with rapidly developing tetraplegia. They were more likely to have an initial diagnosis of GBS and noted to have tremor and/or neuropathic pain more frequently than other groups. Cranial nerve palsies, autonomic dysfunction and respiratory compromise were more frequent and modified Rankin Scale at nadir scores were higher.
Neurophysiological studies showed conduction blockade without temporal dispersion consistent with nodal pathology in the majority of patients. Nerve biopsy in two patients showed axonal loss. There was no obvious improvement to steroids, IVIg, and/or PLEX but slow improvement was noted in patients receiving Rituximab therapy who finally became functionally independent. Fifty percent of patients noted to have malignancy raising the possibility of association with cancer.
Comments: Immune mediated neuropathy is a common treatable neuromuscular condition encountered in clinical practice. Awareness about newer antibodies and associated presentations will help clinicians identify clinical phenotype and offer optimum management.
This study raises an important question about checking these specific antibodies in patients with GBS type acute presentation with severe weakness refractory to first-line treatment. This study described a distinct seropositive immune neuropathy with severe clinical phenotype, which is potentially treatable. Further studies are needed to better describe this distinct entity.
Article of Similar Interest:
Cortese A, Lombardi R, Briani C, et al. Antibodies to neurofascin, contactin-1, and contactin-associated protein 1 in CIDP: Clinical relevance of IgG isotype. Neurol Neuroimmunol Neuroinflamm. 2019 Nov 21;7(1):e639. doi: 10.1212/NXI.0000000000000639