Dilated cardiomyopathy (DCM) is a disease of the myocardium with reduced left ventricular ejection fraction (LVEF). Cardiac
autoantibodies (AAbs) play a causal role in the development and progression of DCM. Removal of AAbs using immunoadsorption (IA/
IgG) has been shown as a therapeutic option to improve cardiac function. However, the response to
therapy differs significantly among patients. The reasons for this variability are not completely understood. Hitherto, no potential
biomarker is available to predict improvement of cardiac function after
therapy accurately. This shotgun
proteome study aims to disclose the differences in the endomyocardial
proteome between patients with improved LVEF after IA/
IgG (responders) and those without improvement (non-responders) before
therapy start. Comparative analysis revealed 54 differentially abundant
proteins that were mostly confined to
carbohydrate and lipid metabolism, energy and immune regulation, and cardioprotection. Selected
proteins representing various functional categories were further confirmed by multiple reaction monitoring (MRM). Among those,
protein S100-A8,
perilipin-4, and kininogen-1 were found the most robust candidates differentiating responders and non-responders. Receiver operating characteristic curve (ROC) analysis of these
proteins revealed highest potential for
protein S100-A8 (AUC 0.92) with high sensitivity and specificity to be developed as a classifier for the prediction of cardiac improvement after IA/
IgG therapy.
SIGNIFICANCE: We evaluated the differences in the myocardial
proteome of responder and non-responder DCM patients before immunoadsorption
therapy and identified a number of differentially abundant
proteins involved in energy and lipid metabolism, immune system, and cardioprotection. MRM was used for verification of results.
Proteins S100-A8,
perilipin-4, and kininogen-1 were found to display the largest differences. The results provide a lead for further studies to screen for
protein biomarker candidates in plasma that might be helpful to stratify patients for immunoadsorption
therapy treatment.