# Anti-pan-neurofascin IgG3: insights about an emerging autoimmune nodoparanodopathy

## TL;DR

This paper reviews a rare and severe autoimmune condition caused by anti-pan-neurofascin IgG3 antibodies, focusing on its clinical challenges and potential treatments.

## Contribution

The paper provides the first comprehensive review of anti-pan-neurofascin IgG3 subtype and its pathophysiological and therapeutic implications.

## Key findings

- Anti-pan-neurofascin IgG3 is associated with severe, rapidly progressing neuropathy and high mortality.
- Eculizumab shows promise as a treatment by inhibiting membrane attack complex formation.
- Standardized diagnostic methods are needed to improve detection and management of this condition.

## 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.