Potential role of antibodies against cardiac Kv channel-interacting protein 2 in dilated cardiomyopathy.
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.
Landsberger
Martin
M
Department of Internal Medicine B, Ernst Moritz Arndt University, Greifswald, Germany. martin.landsberger@uni-greifswald.de
Staudt
Alexander
A
Choudhury
Sangita
S
Trimpert
Christiane
C
Herda
Lars R
LR
Klingel
Karin
K
Kandolf
Reinhard
R
Schultheiss
Heinz-Peter
HP
Kroemer
Heyo K
HK
Völker
Uwe
U
Felix
Stephan B
SB
D000328:Adult; D000818:Animals; D001323:Autoantibodies / Q000378:metabolism*; D002311:Cardiomyopathy, Dilated / Q000276:immunology* / Q000503:physiopathology; D016923:Cell Death / Q000276:immunology; D002478:Cells, Cultured; D015331:Cohort Studies; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051605:Kv Channel-Interacting Proteins / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000276:immunology* / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000276:immunology*; D016133:Polymerase Chain Reaction; D011336:Probability; D051381:Rats; D012016:Reference Values; D012680:Sensitivity and Specificity
D001323:Autoantibodies; D051605:Kv Channel-Interacting Proteins