Autoantibodies Against the Node of Ranvier in Seropositive Chronic Inflammatory Demyelinating Polyneuropathy: Diagnostic, Pathogenic, and Therapeutic Relevance

Front Immunol. 2018 May 14:9:1029. doi: 10.3389/fimmu.2018.01029. eCollection 2018.

Abstract

Discovery of disease-associated autoantibodies has transformed the clinical management of a variety of neurological disorders. Detection of autoantibodies aids diagnosis and allows patient stratification resulting in treatment optimization. In the last years, a set of autoantibodies against proteins located at the node of Ranvier has been identified in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). These antibodies target neurofascin, contactin1, or contactin-associated protein 1, and we propose to name CIDP patients with these antibodies collectively as seropositive. They have unique clinical characteristics that differ from seronegative CIDP. Moreover, there is compelling evidence that autoantibodies are relevant for the pathogenesis. In this article, we review the current knowledge on the characteristics of autoantibodies against the node of Ranvier proteins and their clinical relevance in CIDP. We start with a description of the structure of the node of Ranvier followed by a summary of assays used to identify seropositive patients; and then, we describe clinical features and characteristics linked to seropositivity. We review knowledge on the role of these autoantibodies for the pathogenesis with relevance for the emerging concept of nodopathy/paranodopathy and summarize the treatment implications.

Keywords: autoantibody; chronic inflammatory demyelinating polyneuropathy; contactin; contactin-associated protein 1; neurofascin; node of Ranvier; paranode; seropositive.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoantibodies / immunology*
  • Cell Adhesion Molecules / immunology
  • Cell Adhesion Molecules, Neuronal / immunology
  • Contactin 1 / immunology
  • Humans
  • Mice
  • Nerve Growth Factors / immunology
  • Polyradiculoneuropathy, Chronic Inflammatory Demyelinating / drug therapy*
  • Polyradiculoneuropathy, Chronic Inflammatory Demyelinating / immunology*
  • Ranvier's Nodes / immunology*

Substances

  • Autoantibodies
  • CNTNAP1 protein, human
  • Cell Adhesion Molecules
  • Cell Adhesion Molecules, Neuronal
  • Contactin 1
  • NFASC protein, human
  • Nerve Growth Factors