PT  - JOURNAL ARTICLE
AU  - Grüner, Julia
AU  - Stengel, Helena
AU  - Werner, Christian
AU  - Appeltshauser, Luise
AU  - Sommer, Claudia
AU  - Villmann, Carmen
AU  - Doppler, Kathrin
TI  - Anti–contactin-1 Antibodies Affect Surface Expression and Sodium Currents in Dorsal Root Ganglia
AID  - 10.1212/NXI.0000000000001056
DP  - 2021 Sep 01
TA  - Neurology - Neuroimmunology Neuroinflammation
PG  - e1056
VI  - 8
IP  - 5
4099  - http://nn.neurology.org/content/8/5/e1056.short
4100  - http://nn.neurology.org/content/8/5/e1056.full
SO  - Neurol Neuroimmunol Neuroinflamm2021 Sep 01; 8
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