Journal article
Endomyocardial proteomic signature corresponding to the response of patients with dilated cardiomyopathy to immunoadsorption therapy
Journal of proteomics, Vol.150, pp.121-129
01/06/2017
DOI: 10.1016/j.jprot.2016.09.001
PMID: 27616206
Abstract
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.
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.
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•Exploration of reasons for variation of response of DCM patients to therapy by IA/IgG vary.•Myocardial proteome profiling of responders and non-responders was performed.•Patient subgroups differ in energy and lipid metabolism, immune system and cardioprotection.•Most prominent differences were found for proteins S100-A8, perilipin-4, and kininogen-1.•Biomarker potential of these three proteins was evaluated.
Details
- Title: Subtitle
- Endomyocardial proteomic signature corresponding to the response of patients with dilated cardiomyopathy to immunoadsorption therapy
- Creators
- Gourav Bhardwaj - Universitätsmedizin GreifswaldMarcus Dörr - Universitätsmedizin GreifswaldPraveen Kumar Sappa - Universitätsmedizin GreifswaldSabine Ameling - Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, GermanyVishnu Dhople - Universitätsmedizin GreifswaldLeif Steil - Universitätsmedizin GreifswaldKarin Klingel - University of TübingenKlaus Empen - Universitätsmedizin GreifswaldDaniel Beug - Universitätsmedizin GreifswaldUwe Völker - Universitätsmedizin GreifswaldStephan B. Felix - Universitätsmedizin GreifswaldElke Hammer - Universitätsmedizin Greifswald
- Resource Type
- Journal article
- Publication Details
- Journal of proteomics, Vol.150, pp.121-129
- Publisher
- Elsevier B.V
- DOI
- 10.1016/j.jprot.2016.09.001
- PMID
- 27616206
- ISSN
- 1874-3919
- eISSN
- 1876-7737
- Grant note
- DOI: 10.13039/100010447, name: Deutsches Zentrum für Herz-Kreislaufforschung, award: 81Z7400172; DOI: 10.13039/501100002347, name: Bundesministerium für Bildung und Forschung, award: 03Z1CN22
- Language
- English
- Date published
- 01/06/2017
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984359687202771
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