title: Destruction of paranodal architecture in inflammatory neuropathy with anti-contactin-1 autoantibodies.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurology, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Doppler
authors.affiliation: Department of Neurology, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Luise
authors.initials: L
authors.lastname: Appeltshauser
authors.affiliation: Department of Neurology, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Wilhelmi
authors.affiliation: Institute for Clinical Neurobiology, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Carmen
authors.initials: C
authors.lastname: Villmann
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, USA Center of Neuroscience and Regeneration Research, Veterans Affairs Medical Center, West Haven, USA.
authors.forename: Sulayman D
authors.initials: SD
authors.lastname: Dib-Hajj
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, USA Center of Neuroscience and Regeneration Research, Veterans Affairs Medical Center, West Haven, USA.
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Waxman
authors.affiliation: Department of Neurology, Caritas-Krankenhaus Bad Mergentheim GmbH, Bad Mergentheim, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Mäurer
authors.affiliation: Department of Neurology, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Weishaupt
authors.affiliation: Department of Neurology, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Sommer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D015153:Blotting, Western; D058967:Contactin 1 / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005455:Fluorescent Antibody Technique; D020275:Guillain-Barre Syndrome / Q000276:immunology*; D057809:HEK293 Cells / Q000276:immunology; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D011129:Polyradiculoneuropathy / Q000276:immunology; D020277:Polyradiculoneuropathy, Chronic Inflammatory Demyelinating / Q000276:immunology*; D011901:Ranvier's Nodes / Q000276:immunology*; D055815:Young Adult
chemical_list: D001323:Autoantibodies; C548669:CNTN1 protein, human; D058967:Contactin 1
keywords: GUILLAIN-BARRE SYNDROME; NEUROIMMUNOLOGY; NEUROMUSCULAR; NEUROPATHY; PERIPHERAL NEUROPATHOLOGY