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

Autor:	Doppler K; Department of Neurology, University Hospital Würzburg, Würzburg, Germany., Appeltshauser L; Department of Neurology, University Hospital Würzburg, Würzburg, Germany., Wilhelmi K; Department of Neurology, University Hospital Würzburg, Würzburg, Germany., Villmann C; Institute for Clinical Neurobiology, University Hospital Würzburg, Würzburg, Germany., Dib-Hajj SD; Department of Neurology, Yale University School of Medicine, New Haven, USA Center of Neuroscience and Regeneration Research, Veterans Affairs Medical Center, West Haven, USA., Waxman SG; Department of Neurology, Yale University School of Medicine, New Haven, USA Center of Neuroscience and Regeneration Research, Veterans Affairs Medical Center, West Haven, USA., Mäurer M; Department of Neurology, Caritas-Krankenhaus Bad Mergentheim GmbH, Bad Mergentheim, Germany., Weishaupt A; Department of Neurology, University Hospital Würzburg, Würzburg, Germany., Sommer C; Department of Neurology, University Hospital Würzburg, Würzburg, Germany.
Jazyk:	angličtina
Zdroj:	Journal of neurology, neurosurgery, and psychiatry [J Neurol Neurosurg Psychiatry] 2015 Jul; Vol. 86 (7), pp. 720-8. Date of Electronic Publication: 2015 Feb 18.
DOI:	10.1136/jnnp-2014-309916
Abstrakt:	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. (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)
Databáze:	MEDLINE
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