RT Journal Article
SR Electronic
T1 Destruction of paranodal architecture in inflammatory neuropathy with anti-contactin-1 autoantibodies
JF Journal of Neurology, Neurosurgery & Psychiatry
JO J Neurol Neurosurg Psychiatry
FD BMJ Publishing Group Ltd
SP 720
OP 728
DO 10.1136/jnnp-2014-309916
VO 86
IS 7
A1 Kathrin Doppler
A1 Luise Appeltshauser
A1 Kai Wilhelmi
A1 Carmen Villmann
A1 Sulayman D Dib-Hajj
A1 Stephen G Waxman
A1 Mathias Mäurer
A1 Andreas Weishaupt
A1 Claudia Sommer
YR 2015
UL http://jnnp.bmj.com/content/86/7/720.abstract
AB 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.