Details

Autor(en) / Beteiligte

• Doppler, Kathrin
• Appeltshauser, Luise
• Wilhelmi, Kai
• Villmann, Carmen
• Dib-Hajj, Sulayman D
• Waxman, Stephen G
• Mäurer, Mathias
• Weishaupt, Andreas
• Sommer, Claudia

Titel

Destruction of paranodal architecture in inflammatory neuropathy with anti-contactin-1 autoantibodies

Ist Teil von

• Journal of neurology, neurosurgery and psychiatry, 2015-07, Vol.86 (7), p.720-728

Ort / Verlag

England: BMJ Publishing Group LTD

Erscheinungsjahr

2015

Link zum Volltext

Quelle

BMJ Journals Archiv - DFG Nationallizenzen

Beschreibungen/Notizen

• ObjectiveAutoantibodies 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).MethodsWe 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.ResultsHigh 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.InterpretationWe 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.