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

Sep 29, 2026

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Neurofascin family proteins drive a spectrum of autoimmune nodoparanodopathies as CIDP subtypes emerge with distinct mechanisms. Among them, anti-pan-neurofascin IgG3 shows a particularly severe, diagnostically challenging phenotype, often with fulminant progression and high morbidity and mortality. This review summarizes seven reported cases and proposes a pathophysiology centered on Ranvier node destruction via hyperactivated membrane attack complex (MAC) formation. It also evaluates emerging evidence for eculizumab and discusses standardized antibody assays, serology, and neurophysiology to improve diagnosis.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages8

Reading Time20 min

AccessFree to download

Abstract

Keywords

Introduction

Node of Ranvier dysfunction classification

Neurofascin isoforms and antibody targets

Autoimmune nodopathies and treatment guidelines

Article published online: 2025-10-15 Review Article 1 Anti-pan-neurofascin IgG3: insights about an emerging autoimmune nodoparanodopathy Gabriel Erzinger 1 Mayra Emi Guinoza Inushi 1 Laura Fiuza Parolin 1 Gabriel de Deus Vieira 1 Marcus Vinícius Magno Gonçalves 1 1 Universidade da Região de Joinville, Departamento de Medicina, Joinville SC, Brazil. Arq. Neuro-Psiquiatr. 2025;83(9):s00451812035 . Address for correspondence Gabriel Erzinger (email: [gabierzinger@gmail.com](gabierzinger@gmail.com)) Abstract Keywords ► Polyneuropathies ► Autoantibodies ► Immunoglobulin G 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. INTRODUCTION In 2013, Uncini et al.1 proposed a new classiﬁcation for dysfunctions of the node of Ranvier, termed nodoparanodopathy, initially described in antiganglioside antibody-mediated neuropathies. This classiﬁcation differs from the traditional demyelinating and axonal classiﬁcations, focusing on the speciﬁc site of action, such as the node, paranode, juxtaparanode, or internode regions. The previous classiﬁ cation divides polyneuropathies into two groups: the ﬁrst affects the myelin/Schwann cells, and the second affects the received January 7, 2025 received in its ﬁnal form May 23, 2025 accepted July 27, 2025 DOI [https://doi.org/](https://doi.org/)[ ](https://doi.org/)10.1055/s-0045-1812035 . ISSN 0004-282X. Editor-in-Chief: Ayrton Roberto Massaro. Associate Editor: Wilson Marques Jr. axon, which often leads to imprecise diagnoses in some electrophysiological ﬁndings, particularly in Guillain-Barré syndrome (GBS) subtypes. This paradigm shift is signiﬁcant as it provides a more precise correlation between clinical presentation and underlying pathophysiological mechanisms, challenging the notion that the nodal region is the sole pathological target and the misconception of a universally-poor prognosis in such diseases.1 Furthemore, in those [regions. an](regions. an) antibody target of relevance to the clinical practice is the neurofascin (NF) family of proteins, ﬁrst described in 1987 in chicks. These neural surface proteins © 2025 . The Author(s) . This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit ([https://creativecommons.org/licenses/by/4.0/](https://creativecommons.org/licenses/by/4.0/)) Thieme Revinter Publicações Ltda. , Rua Rego Freitas, 175, loja 1, República, São Paulo, SP, CEP 01220-010, Brazil 2 Anti-pan-neurofascin IgG3: a review Erzinger et al. have several i

FAQs

What is anti-pan-neurofascin IgG3 and why is it clinically important?

Anti-pan-neurofascin IgG3 is a subtype of antibody-mediated autoimmune nodoparanodopathy. It is highlighted for a severe, diagnostically challenging course with high morbidity and mortality.

How does the review explain the proposed mechanism of disease in anti-pan-neurofascin IgG3?

The review proposes destruction of the node of Ranvier through hyperactivation of membrane attack complex (MAC) formation.

What diagnostic and treatment approaches does the review emphasize?

It discusses using standardized antibody assays, serological analyses, and neurophysiological studies to improve diagnostic accuracy, and it examines emerging evidence for eculizumab alongside other treatment strategies.

Sep 29, 2026

Uploaded by Finn