科研之友
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摘要
Autoimmune-associated proarrhythmia in dilated cardiomyopathy (DCM) is poorly understood. Given the significance of KCNQ1 potassium channels in heart rhythm disorders, we hypothesized that circulating anti-KCNQ1 autoantibodies directly modulate cardiac electrophysiology in DCM patients. The purpose of this pilot study was to characterize ion channel autoantibodies in DCM targeting the cardiac repolarizing K current, I-Ks, and the underlying KCNQ1 potassium channel. One hundred and fifty DCM patients were screened for anti-KCNQ1 autoantibodies using an enzyme-linked immunosorbent assay. Autoantibodies targeting the extracellular pore domain of the KCNQ1 channel were detected in 6 of study patients. Seropositive individuals exhibited significantly shorter corrected QT intervals when compared with seronegative patients (371 39.9 ms vs. 408 47.9 ms; P 0.036). There was no difference in clinical severity of heart failure between groups. The functional significance of anti-KCNQ1 antibodies was determined in human embryonic kidney 293 cells expressing KCNQ1/KCNE1 using the whole-cell patch clamp technique. I-Ks recordings demonstrated a 2.7-fold increase in mean current density on exposure to patients sera containing anti-KCNQ1 antibodies in contrast to seronegative controls (8.74 1.44 pA/pF vs. 3.26 0.36 pA/pF; P 0.003). I-Ks enhancement was not associated with increased KCNQ1 protein levels or altered cell surface expression of the channel. Anti-KCNQ1 autoantibodies found in a subgroup of DCM patients are associated with QT interval shortening and increased I-Ks current.
- 出版日期2013-6-1
