Abstract
Neurofascin constitutes a family of cell-surface proteins identified more than 4 decades
ago, produced through alternative RNA splicing, with various isoforms expressed in
neural tissues. With the emergence of chronic inflammatory demyelinating polyneuropathy
(CIDP) subtypes characterized by distinct pathological mechanisms, antineurofascin
antibody-mediated neuropathies have gained attention and are now categorized as autoimmune
nodoparanodopathies. Among these, the anti-pan-neurofascin immunoglobulin G3 (IgG3)
subtype presents a particularly severe and diagnostically-challenging phenotype, marked
by a fulminant clinical course, diverse symptomatology, and high rates of morbidity
and mortality. Despite its clinical relevance, to date, no comprehensive review has
focused specifically on this manifestation, highlighting a significant gap in the
literature. To address this, we herein review the seven reported cases and explore
the proposed pathophysiological mechanism involving the destruction of the node of
Ranvier via hyperactivation of membrane attack complex (MAC) formation. Additionally,
we examine emerging evidence supporting the use of eculizumab as a potential therapeutic
option, alongside other treatment strategies. Finally, we discuss the role of standardized
antibody assays, serological analyses, and neurophysiological studies in improving
diagnostic accuracy.
Keywords
Polyneuropathies - Autoantibodies - Immunoglobulin G
Bibliographical Record
Gabriel Erzinger, Mayra Emi Guinoza Inushi, Laura Fiuza Parolin, Gabriel de Deus Vieira,
Marcus Vinícius Magno Gonçalves. Anti-pan-neurofascin IgG3: insights about an emerging
autoimmune nodoparanodopathy. Arq Neuropsiquiatr 2025; 83: s00451812035.
DOI: 10.1055/s-0045-1812035
