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Research paper
Neurofascin-155 IgM autoantibodies in patients with inflammatory neuropathies
  1. Kathrin Doppler1,
  2. Helena Stengel1,
  3. Luise Appeltshauser1,
  4. Julian Grosskreutz2,
  5. Judy King Man Ng3,
  6. Edgar Meinl3,
  7. Claudia Sommer1
  1. 1 Department of Neurology, University Hospital Würzburg, Josef-Schneider-Str. 11, 97080, Würzburg, Germany
  2. 2 Department of Neurology, University Hospital Jena, Jena, Germany
  3. 3 Institute of Clinical Neuroimmunology, Ludwig-Maximilians-University, Munich, Germany
  1. Correspondence to Dr Kathrin Doppler, Department of Neurology, University Hospital Würzburg, Josef-Schneider-Str. 11, 97080, Würzburg, Germany; Doppler_K{at}ukw.de

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.

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Footnotes

  • Contributors KD: study conception and design, analysis and interpretation of data, writing of the manuscript. HS: performance of experiments, data collection and analysis, revision of the manuscript. LA: performance of experiments, data collection and analysis, revision of the manuscript. JG: data collection and analysis. JKMN: study conception. EM: study conception, interpretation of data, revision of the manuscript. CS: study conception and design, interpretation of data, revision of the manuscript.

  • Funding The study was funded by a grant of Kedrion International GmbH (KD, CS) and the German KKNMS (Kompetenznetz Multiple Sklerose) (EM).

  • Competing interests KD received personal fees from Baxter/Baxalta and Grifols. EM received personal fees from Roche, Novartis and Genzyme and grants outside the submitted work from Novartis and Genzyme. CS received personal fees from Air Liquide, Alnylam, Astellas, Baxalta, CSL Behring, Genzyme, Grifols, Pfizer, UCB and Kedrion.

  • Patient consent Parental/guardian consent obtained.

  • Ethics approval Ethic's committee of the University of Würzburg.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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