Myocardial gene expression profiles and cardiodepressant autoantibodies predict response of patients with dilated cardiomyopathy to immunoadsorption therapy

Background: Immunoadsorption with subsequent IgG substitution (IA/IgG) represents a novel therapeutic approach in treatment of dilated cardiomyopathy (DCM) which leads to improvement of left ventricular ejection fraction (LVEF). However, response to this therapeutic intervention shows wide inter-individual variability. In this pilot study, we tested the value of clinical, biochemical and molecular parameters for prediction of the response of patients with DCM to IA/IgG. Methods & Results: Forty DCM patients underwent endomyocardial biopsies (EMBs) before IA/IgG. In 8 patients with normal LVEF (controls) EMB were obtained for clinical reasons. Clinical parameters, negative inotropic activity (NIA) of antibodies on isolated rat cardiomyocytes and gene expression profiles of EMBs were analyzed. DCM patients displaying improvement of LVEF (≥ 20% relative and ≥ 5% absolute) six month after IA/IgG were considered responders. Compared to non-responders (n=16), responders (n=24) displayed shorter disease duration (p=0.006), smaller LV internal diameter in diastole (LVIDd) (p=0.019) and stronger NIA of antibodies. Antibodies obtained from controls were devoid of NIA. Myocardial gene expression patterns were different in responders and non-responders for genes of oxidative phosphorylation, mitochondrial dysfunction, hypertrophy, and ubiquitin proteasome pathway. Integration of scores of NIA and expression levels of four genes allowed robust discrimination of responders from non-responders at baseline (sensitivity of 100 % (95% CI, 85.8%-100%); specificity up to 100% (95 % CI, 79.4%-100%, cut-off value: -0.28), and was superior to scores derived from antibodies, gene expression or clinical parameters only. Conclusion: Combined assessment of NIA of antibodies and gene expression patterns of DCM patients at baseline predicts response to IA/IgG therapy and may enable appropriate selection of patients who benefit from this therapeutic intervention. EMBs of 40 DCM patients at baseline (before IA/IgG), as well as 8 controls, were used for transcriptional profiling using Affymetrix HGU 133 Plus 2.0.