title: Autoantibodies detected to expressed K+ channels are implicated in neuromyotonia.
abstract: 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.
authors.affiliation: Neurosciences Group, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: I K
authors.initials: IK
authors.lastname: Hart
authors.forename: C
authors.initials: C
authors.lastname: Waters
authors.forename: A
authors.initials: A
authors.lastname: Vincent
authors.forename: C
authors.initials: C
authors.lastname: Newland
authors.forename: D
authors.initials: D
authors.lastname: Beeson
authors.forename: O
authors.initials: O
authors.lastname: Pongs
authors.forename: C
authors.initials: C
authors.lastname: Morris
authors.forename: J
authors.initials: J
authors.lastname: Newsom-Davis
mesh_terms: D001323:Autoantibodies / Q000032:analysis*; D005207:Fasciculation / Q000378:metabolism*; D006801:Humans; D015221:Potassium Channels / Q000378:metabolism*
chemical_list: D001323:Autoantibodies; D015221:Potassium Channels