Autoantibodies detected to expressed K+ channels are implicated in neuromyotonia.
Antibody-mediated autoimmunity underlies a diverse range of disorders, particularly in the nervous system where the extracellular domains of ion channels and receptors are especially vulnerable targets. We present here a novel means of detecting autoantibodies where the genes of the suspected target proteins are known, and use it to detect specific autoantibodies in acquired neuromyotonia (Isaacs' syndrome), a disorder characterized by hyperexcitable motor nerves and sometimes by central abnormalities. We expressed different human brain voltage-gated potassium channels in Xenopus oocytes by injecting the relevant alpha-subunit complementary RNA, and detected antibody binding by immunohistochemistry on frozen sections. Antibodies were detected to one or more human brain voltage-gated potassium channel in 12 of 12 neuromyotonia patients and none of 18 control subjects. The results establish neuromyotonia as a new antibody-mediated channelopathy and indicate the investigative potential of this molecular immunohistochemical assay.
Hart
I K
IK
Neurosciences Group, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom.
Waters
C
C
Vincent
A
A
Newland
C
C
Beeson
D
D
Pongs
O
O
Morris
C
C
Newsom-Davis
J
J
D001323:Autoantibodies / Q000032:analysis*; D005207:Fasciculation / Q000378:metabolism*; D006801:Humans; D015221:Potassium Channels / Q000378:metabolism*
D001323:Autoantibodies; D015221:Potassium Channels