Autoantibodies to nodal isoforms of neurofascin in chronic inflammatory demyelinating polyneuropathy.

Abstract

Chronic inflammatory demyelination polyneuropathy is a heterogeneous and treatable immune-mediated disorder that lacks biomarkers to support diagnosis. Recent evidence indicates that paranodal proteins (contactin 1, contactin-associated protein 1, and neurofascin-155) are the targets of autoantibodies in subsets of patients showing distinct clinical presentations. Here, we identified neurofascin-186 and neurofascin-140 as the main targets of autoantibodies in five patients presenting IgG reactivity against the nodes of Ranvier. Four patients displayed predominantly IgG4 antibodies, and one patient presented IgG3 antibodies that activated the complement pathway in vitro. These patients present distinct clinical features compared to those with anti-neurofascin-155 IgG4. Most patients had a severe phenotype associated with conduction block or decreased distal motor amplitude. Four patients had a subacute-onset and sensory ataxia. Two patients presented with nephrotic syndromes and one patient with an IgG4-related retroperitoneal fibrosis. Intravenous immunoglobulin and corticosteroids were effective in three patients, and one patient remitted following rituximab treatment. Clinical remission was associated with autoantibody depletion and with recovery of conduction block and distal motor amplitude suggesting a nodo-paranodopathy. Our data demonstrate that the pathogenic mechanisms responsible for chronic inflammatory demyelination polyneuropathy are broad and may include dysfunctions at the nodes of Ranvier in a subgroup of patients.

• Authors: Emilien Delmont, Constance Manso, Luis Querol, Andrea Cortese, Angela Berardinelli, Alessandro Lozza, Maya Belghazi, Pauline Malissart, Pierre Labauge, Guillaume Taieb, Nobuhiro Yuki, Isabel Illa, Shahram Attarian, Jérôme J Devaux
• Journal: Brain : a journal of neurology (Brain) Vol. 140 Issue 7 Pg. 1851-1858 (Jul 01 2017) ISSN: 1460-2156 [Electronic] England
• PMID: 28575198 (Publication Type: Journal Article)
• Copyright: © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: [email protected].

Chemical References

• Adrenal Cortex Hormones
• Autoantibodies
• Cell Adhesion Molecules
• Immunoglobulins, Intravenous
• NFASC protein, human
• Nerve Growth Factors
• Protein Isoforms
• Rituximab

Topics

• Adolescent
• Adrenal Cortex Hormones (therapeutic use)
• Adult
• Aged
• Aged, 80 and over
• Autoantibodies (blood, immunology)
• Case-Control Studies
• Cell Adhesion Molecules (immunology)
• Child
• Child, Preschool
• Female
• Humans
• Immunoglobulins, Intravenous (therapeutic use)
• Male
• Middle Aged
• Nerve Growth Factors (immunology)
• Neural Conduction (physiology)
• Polyradiculoneuropathy, Chronic Inflammatory Demyelinating (blood, drug therapy, immunology)
• Protein Isoforms (immunology)
• Ranvier's Nodes (immunology)
• Rituximab (therapeutic use)
• Young Adult