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 α‐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.