Abstract 2196: Anti-KCNH2 Antibody-induced Long QT Syndrome -Novel Acquired Form of LQT Syndrome-
Background: The KCNH2 (HERG) channel is sensitive to various conditions such as hypokalemia, bradycardia and drugs. However, the autoimmune effect on the KCNH2 channel has not been elucidated. The purpose of this study was to examine whether autoimmune abnormality causes the acquired form of long QT syndrome (LQTS).
Methods and Results: Here we report a 42-year-old female patient with acquired LQTS who did not have any known cause of QT prolongation but had increased immunoglobulin G (IgG) concentration and positive anti-SSA/Ro antibodies. Screening for mutations in LQTS-associated genes was carried out by PCR-DNA conformation polymorphism analysis and DNA sequencing. No mutation was detected in any of the exons of KCNQ1, KCNH2 (HERG), SCN5A, KCNE1 and KCNE2. Effects of the patient’s serum and IgG on KCNH2 currents were examined by the patch clamp technique. KCNH2 (HERG) current stably expressed in HEK 293 cells was significantly reduced when the culture medium was supplemented with the patient’s serum and IgG (Figure⇓). However, HERG current was not reduced in the presence of serum and IgG from healthy control subjects. The patient’s serum had no effect on the slowly activating delayed rectifier K+ currents (IKs) of HEK 293 cells expressing KCNQ1/KCNE1. Western blot analysis revealed that the patient’s IgG included autoantibodies against KCNH2 (HERG) protein.
Conclusion: Anti-KCNH2 antibody from a patient with acquired LQTS reduced the KCNH2 (HERG) current. This autoimmunity against KCNH2 (HERG) represents a novel cause of the acquired form of LQTS.