Neurofascin-155 IgM autoantibodies in patients with inflammatory neuropathies

J Neurol Neurosurg Psychiatry. 2018 Nov;89(11):1145-1151. doi: 10.1136/jnnp-2018-318170. Epub 2018 Jun 26.

Abstract

Objectives: Recently, IgG autoantibodies against different paranodal proteins have been detected and this has led to important advances in the management of inflammatory neuropathies. In contrast, not much is known on IgM autoantibodies against paranodal proteins.

Methods: In the present study, we screened a large cohort of patients (n=140) with inflammatory neuropathies for IgM autoantibodies against neurofascin-155, neurofascin-186 or contactin-1.

Results: IgM autoantibodies against neurofascin-155 were detected by ELISA in five patients, four with inflammatory demyelinating polyradiculoneuropathy (CIDP) and one with Guillain-Barré syndrome (GBS), and were confirmed by ELISA-based preabsorption experiments and Western blot. Titres ranged from 1:100 to 1:400. We did not detect IgM anti-neurofascin-186 or anti-contactin-1 antibodies in this cohort. All patients presented with distally accentuated tetraparesis and hypesthesia. Remarkably, tremor was present in three of the patients with CIDP and occurred in the patients with GBS after the acute phase of disease. Nerve conduction studies revealed prolonged distal motor latencies and F wave latencies. Nerve biopsies showed signs of secondary axonal damage in three of the patients, demyelinating features in one patient. Teased fibre preparations did not demonstrate paranodal damage.

Conclusion: In summary, IgM neurofascin-155 autoantibodies may be worth testing in patients with inflammatory neuropathies. Their pathogenic role needs to be determined in future experiments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Autoantibodies / blood*
  • Cell Adhesion Molecules / immunology*
  • Contactin 1 / immunology
  • Female
  • Guillain-Barre Syndrome / blood
  • Guillain-Barre Syndrome / immunology*
  • Humans
  • Immunoglobulin M / blood*
  • Male
  • Middle Aged
  • Nerve Growth Factors / immunology*
  • Young Adult

Substances

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