title: Anti-KCNQ1 K⁺ channel autoantibodies increase IKs current and are associated with QT interval shortening in dilated cardiomyopathy.
abstract: OBJECTIVE
  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, IKs, and the underlying KCNQ1 potassium channel.
  
  
  RESULTS
  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. IKs 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). IKs enhancement was not associated with increased KCNQ1 protein levels or altered cell surface expression of the channel.
  
  
  CONCLUSIONS
  Anti-KCNQ1 autoantibodies found in a subgroup of DCM patients are associated with QT interval shortening and increased IKs current.
authors: Department of Cardiology, University Hospital of Heidelberg, Im Neuenheimer Feld 410, Heidelberg 69120, Germany.
authors: Jin
authors: J
authors: Li
authors: Claudia
authors: C
authors: Seyler
authors: Felix
authors: F
authors: Wiedmann
authors: Constanze
authors: C
authors: Schmidt
authors: Patrick A
authors: PA
authors: Schweizer
authors: Rüdiger
authors: R
authors: Becker
authors: Hugo A
authors: HA
authors: Katus
authors: Dierk
authors: D
authors: Thomas
mesh_terms: D000200:Action Potentials; D000328:Adult; D000368:Aged; D001145:Arrhythmias, Cardiac / Q000097:blood / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D001323:Autoantibodies / Q000097:blood*; D002311:Cardiomyopathy, Dilated / Q000097:blood / Q000150:complications / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D004562:Electrocardiography; D005260:Female; D057809:HEK293 Cells; D006329:Heart Conduction System / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D013997:Time Factors; D014162:Transfection
chemical_list: D001323:Autoantibodies; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human
keywords: Antibody; Delayed rectifier potassium current; Dilated cardiomyopathy; KCNQ1; Short QT interval