RT Journal Article
SR Electronic
T1 Anti–contactin-1 Antibodies Affect Surface Expression and Sodium Currents in Dorsal Root Ganglia
JF Neurology - Neuroimmunology Neuroinflammation
JO Neurol Neuroimmunol Neuroinflamm
FD Lippincott Williams & Wilkins
SP e1056
DO 10.1212/NXI.0000000000001056
VO 8
IS 5
A1 Julia Grüner
A1 Helena Stengel
A1 Christian Werner
A1 Luise Appeltshauser
A1 Claudia Sommer
A1 Carmen Villmann
A1 Kathrin Doppler
YR 2021
UL http://nn.neurology.org/content/8/5/e1056.abstract
AB Background and Objectives As autoantibodies to contactin-1 from patients with chronic inflammatory demyelinating polyradiculoneuropathy not only bind to the paranodes where they are supposed to cause conduction failure but also bind to other neuronal cell types, we aimed to investigate the effect of anti–contactin-1 autoantibodies on contactin-1 surface expression in cerebellar granule neurons, dorsal root ganglion neurons, and contactin-1–transfected human embryonic kidney 293 cells.Methods Immunocytochemistry including structured illumination microscopy and immunoblotting was used to determine expression levels of contactin-1 and/or sodium channels after long-term exposure to autoantibodies from 3 seropositive patients. For functional analysis of sodium channels, whole-cell recordings of sodium currents were performed on dorsal root ganglion neurons incubated with anti–contactin-1 autoantibodies.Results We found a reduction in contactin-1 expression levels on dorsal root ganglion neurons, cerebellar granule neurons, and contactin-1–transfected human embryonic kidney 293 cells and decreased dorsal root ganglion sodium currents after long-term exposure to anti–contactin-1 autoantibodies. Sodium channel density did not decrease.Discussion Our results demonstrate a direct effect of anti–contactin-1 autoantibodies on the surface expression of contactin-1 and sodium currents in dorsal root ganglion neurons. This may be the pathophysiologic correlate of sensory ataxia reported in these patients.CGN=cerebellar granular neuron; CNTN1=contactin-1; DRG=dorsal root ganglia; HC=healthy control; LDH=lactate dehydrogenase; SIM=structured illumination microscopy; 2R=2-day recovery phase