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.