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 pres ent 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 disord er characterized by hyperexcitable motor nerves and sometimes by-centr al abnormalities. We expressed different human brain voltage-gated pot assium channels in Xenopus oocytes by injecting the relevant ol-subuni t complementary RNA, and detected antibody binding by immunohistochemi stry on frozen sections. Antibodies were detected to one or more human brain voltage-gated potassium channel in 12 of 12 neuromyotonia patie nts and none of 18 control subjects. The results establish neuromyoton ia as a new antibody-mediated channelopathy and indicate the investiga tive potential of this molecular immunohistochemical assay.