Abstract 2964: Auto-Antibodies Against Cardiac KChIP2.6 are Associated with Dilated and Ischemic Cardiomyopathy
BACKGROUND: Growing evidence suggests that autoimmune mechanisms may participate in the pathogenesis of dilated cardiomyopathy (DCM). Previously, we identified auto-antibodies against the brain Kv channel interacting protein 1 (KChIP1) in sera from DCM patients by protein array screening. In hearts and endothelial cells, KChIP2 is the predominantly expressed form and exists in 8 different isoforms reflecting splice variants. We analysed the distribution of auto-antibodies against the isoform 6 (KChIP2.6), and two known targets of auto-antibodies, cardiac troponin I (cTnI), and the beta1-adrenergic receptor in sera from patients with DCM or ischemic cardiomyopathy (ICM), and control subjects.
METHODS: The coding sequence of cardiac KChIP2.6 was cloned by RT-PCR and fused in frame to the strep-tag coding sequence of pASK-IBA7. KChIP2.6 was expressed in E .coli ER256 and purified by affinity chromatography. IgG fractions were purified from plasma of patients with DCM (n = 104) or ICM (n = 60; matched for age, gender, NYHA functional classes II to IV, and LVEF < 40%) and from control subjects (n = 104) by affinity chromatography. Relative binding units to recombinant KChIP2.6, cTnI and beta1-receptor (synthetic peptide of the second extra-cellular loop) were determined by surface plasmon resonance on a BIAcore® X.
RESULTS: 53.8% of the DCM samples, 41.7% of the ICM samples, and 12.5% of the control samples were positive for at least one of the auto-antibodies tested. In detail, we detected auto-antibodies against cardiac KChIP2.6 in 13.5% (14 of 104) of the DCM samples, 10.0% (6 of 60) of the ICM samples, and in 3.8% (4 of 104) of the control samples. Anti-beta1-adrenergic and anti-cTnI antibodies were also significantly more frequent in DCM and ICM samples than in control samples (see table⇓).
CONCLUSIONS: Humoral immunity is disturbed in DCM and ICM patients. Auto-antibodies against cardiac KChIP2.6 appear to be associated with dilated and ischemic cardiomyopathy.