Potential role of antibodies against cardiac Kv channel-interacting protein 2 in dilated cardiomyopathy

Am Heart J. 2008 Jul;156(1):92-99.e2. doi: 10.1016/j.ahj.2008.02.015. Epub 2008 May 16.

Abstract

Background: Growing evidence suggests participation of autoimmune mechanisms in the pathogenesis of dilated cardiomyopathy (DCM).

Methods: Patients with heart failure (left ventricular ejection fraction < or =50%) due to DCM (n = 98) or ischemic cardiomyopathy (ICM, n = 49) and controls with normal left ventricular function (n = 98) were included. Immunoglobulin G antibodies were purified from plasma by affinity chromatography and analyzed by surface plasmon resonance analysis. We analyzed the distribution of autoantibodies against Kv channel-interacting protein (KChIP) 2.6, cardiac troponin I (cTnI), and the beta1-adrenergic receptor (second extracellular loop, cardiac beta1-adrenergic receptor [SEL-beta1-AR])-two other known autoantibodies involved in heart failure. Effects of antibodies against KChIP2 on cell death of isolated rat cardiomyocytes were assessed by flow cytometry.

Results: We detected autoantibodies against KChIP2.6 in 14.3% (P < .015 vs controls, P = .286 vs ICM) of the DCM samples, in 8.2% of the ICM samples (P = .304 vs controls), and in 4.1% of the control samples. Virus persistence was significantly associated with detection of autoantibodies against KChIP2.6 in DCM patients (P = .025). Antibodies against SEL-beta1-AR were more frequent in DCM samples (34.7%, P < .001 vs controls, P = .02 vs ICM) and ICM samples (16.3%, P = .083 vs control) than in control samples (7.1%). Antibodies against cTnI were more frequent in DCM samples (20.4%, P < .001 vs controls, P = .769 vs ICM) and in ICM samples (18.4%, P < .01 vs controls) than in control samples (4.1%). Antibodies against rat KChIP2 enhanced cell death in isolated rat cardiomyocytes. Immunofluorescence indicated cell surface expression of KChIP2.

Conclusions: Autoantibodies against KChIP2.6, SEL-beta1-AR, and cTnI appear to be associated with DCM. Antibodies against KChIP2 may enhance cell death of rat cardiomyocytes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Autoantibodies / metabolism*
  • Cardiomyopathy, Dilated / immunology*
  • Cardiomyopathy, Dilated / physiopathology
  • Cell Death / immunology
  • Cells, Cultured
  • Cohort Studies
  • Female
  • Flow Cytometry
  • Humans
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Kv Channel-Interacting Proteins / immunology
  • Kv Channel-Interacting Proteins / metabolism*
  • Male
  • Middle Aged
  • Myocardial Ischemia / immunology*
  • Myocardial Ischemia / physiopathology
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / immunology*
  • Polymerase Chain Reaction
  • Probability
  • Rats
  • Reference Values
  • Sensitivity and Specificity

Substances

  • Autoantibodies
  • Kv Channel-Interacting Proteins