Paranodal dissection in chronic inflammatory demyelinating polyneuropathy with anti-neurofascin-155 and anti-contactin-1 antibodies

J Neurol Neurosurg Psychiatry. 2017 Jun;88(6):465-473. doi: 10.1136/jnnp-2016-314895. Epub 2017 Jan 10.

Abstract

Objective: To investigate the morphological features of chronic inflammatory demyelinating polyneuropathy (CIDP) with autoantibodies directed against paranodal junctional molecules, particularly focusing on the fine structures of the paranodes.

Methods: We assessed sural nerve biopsy specimens obtained from 9 patients with CIDP with anti-neurofascin-155 antibodies and 1 patient with anti-contactin-1 antibodies. 13 patients with CIDP without these antibodies were also examined to compare pathological findings.

Results: Characteristic light and electron microscopy findings in transverse sections from patients with anti-neurofascin-155 and anti-contactin-1 antibodies indicated a slight reduction in myelinated fibre density, with scattered myelin ovoids, and the absence of macrophage-mediated demyelination or onion bulbs. Teased-fibre preparations revealed that segmental demyelination tended to be found in patients with relatively higher frequencies of axonal degeneration and was tandemly found at consecutive nodes of Ranvier in a single fibre. Assessment of longitudinal sections by electron microscopy revealed that detachment of terminal myelin loops from the axolemma was frequently found at the paranode in patients with anti-neurofascin-155 and anti-contactin-1 antibody-positive CIDP compared with patients with antibody-negative CIDP. Patients with anti-neurofascin-155 antibodies showed a positive correlation between the frequencies of axo-glial detachment at the paranode and axonal degeneration, as assessed by teased-fibre preparations (p<0.05).

Conclusions: Paranodal dissection without classical macrophage-mediated demyelination is the characteristic feature of patients with CIDP with autoantibodies to paranodal axo-glial junctional molecules.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Autoantibodies / analysis*
  • Axons / immunology
  • Axons / pathology*
  • Biopsy
  • Cell Adhesion Molecules / immunology*
  • Contactin 1 / immunology*
  • Female
  • Humans
  • Male
  • Microscopy, Electron
  • Middle Aged
  • Myelin Sheath / immunology
  • Myelin Sheath / pathology*
  • Nerve Growth Factors / immunology*
  • Neuroglia / immunology
  • Neuroglia / pathology*
  • Polyradiculoneuropathy, Chronic Inflammatory Demyelinating / immunology
  • Polyradiculoneuropathy, Chronic Inflammatory Demyelinating / pathology*
  • Ranvier's Nodes / immunology
  • Ranvier's Nodes / pathology*
  • Schwann Cells / immunology
  • Schwann Cells / pathology
  • Sural Nerve / immunology
  • Sural Nerve / pathology*
  • Young Adult

Substances

  • Autoantibodies
  • CNTN1 protein, human
  • Cell Adhesion Molecules
  • Contactin 1
  • NFASC protein, human
  • Nerve Growth Factors