Use of Biomarkers for the Prediction of Treatment Response: Immunoadsorption in Dilated Cardiomyopathy as a Clinical Example

Abstract

In this chapter, we outline a clinical example illustrating how integrated analyses of biomarkers might be used for the prediction of treatment response. We report findings from a pilot study that investigated the hemodynamic effects of a novel treatment option, immunoadsorption with subsequent IgG substitution (IA/IgG), in patients with dilated cardiomyopathy. Several previous studies have shown that this treatment leads to a significant improvement of cardiac function and relief of symptoms. Response to this therapy is, however, characterized by a wide inter-individual variability. In a pilot study, we tested the value of clinical, biochemical and molecular parameters for prediction of the response to IA/IgG. This study demonstrated that combined assessment of two markers (negative inotropic activity of antibodies in the blood and gene expression patterns derived from myocardial biopsies) predicts response to this therapy with an extremely high sensitivity and specificity, thereby enabling appropriate selection of patients who most likely benefit from this therapeutic intervention. Further studies will screen for biomarker signatures in blood, which do not depend on endomyocardial biopsies, and will compare responders and non-responders with respect to other molecular markers (e.g. plasma proteome, metabolome and microRNA profiles as well as whole blood transcriptome signatures). In the future, such strategies might facilitate selection of patients with dilated cardiomyopathy who are responders not only to immunoadsorption therapy but also to other heart failure treatments for which a heterogeneous response is observed and thus will help to offer more effective treatments to affected patients.