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Research paper
Destruction of paranodal architecture in inflammatory neuropathy with anti-contactin-1 autoantibodies
  1. Kathrin Doppler1,
  2. Luise Appeltshauser1,
  3. Kai Wilhelmi1,
  4. Carmen Villmann2,
  5. Sulayman D Dib-Hajj3,4,
  6. Stephen G Waxman3,4,
  7. Mathias Mäurer5,
  8. Andreas Weishaupt1,
  9. Claudia Sommer1
  1. 1Department of Neurology, University Hospital Würzburg, Würzburg, Germany
  2. 2Institute for Clinical Neurobiology, University Hospital Würzburg, Würzburg, Germany
  3. 3Department of Neurology, Yale University School of Medicine, New Haven, USA
  4. 4Center of Neuroscience and Regeneration Research, Veterans Affairs Medical Center, West Haven, USA
  5. 5Department of Neurology, Caritas-Krankenhaus Bad Mergentheim GmbH, Bad Mergentheim, 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

Objective Autoantibodies against paranodal proteins have been described in patients with inflammatory neuropathies, but their association with pathology of nodes of Ranvier is unclear. We describe the clinical phenotype and histopathological changes of paranodal architecture of patients with autoantibodies against contactin-1, identified from a cohort with chronic inflammatory demyelinating polyradiculoneuropathy (n=53) and Guillain-Barré syndrome (n=21).

Methods We used ELISA to detect autoantibodies against contactin-1. Specificity of the autoantibodies was confirmed by immunoblot assay, binding to contactin-1-transfected human embryonic kidney cells, binding to paranodes of murine teased fibres and preabsorption experiments. Paranodal pathology was investigated by immunofluorescence labelling of dermal myelinated fibres.

Results High reactivity to contactin-1 by ELISA was found in four patients with chronic inflammatory demyelinating polyradiculoneuropathy and in none of the patients with Guillain-Barré syndrome, which was confirmed by cell binding assays in all four patients. The four patients presented with a typical clinical picture, namely acute onset of disease and severe motor symptoms, with three patients manifesting action tremor. Immunofluorescence-labelling of paranodal proteins of dermal myelinated fibres revealed disruption of paranodal architecture. Semithin sections showed axonal damage but no classical signs of demyelination.

Interpretation We conclude that anti-contactin-1-related neuropathy constitutes a presumably autoantibody-mediated form of inflammatory neuropathy with distinct clinical symptoms and disruption of paranodal architecture as a pathological correlate. Anti-contactin-1-associated neuropathy does not meet morphological criteria of demyelinating neuropathy and therefore, might rather be termed a ‘paranodopathy’ rather than a subtype of demyelinating inflammatory neuropathy.

  • PERIPHERAL NEUROPATHOLOGY
  • NEUROPATHY
  • NEUROMUSCULAR
  • NEUROIMMUNOLOGY
  • GUILLAIN-BARRE SYNDROME

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