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.