“The Role of Monocytes in Autoimmune Myocarditis” – December 2007

For a long time, our laboratory under the leadership of Dr. Noel Rose has been engaged in studying the mechanisms by which inflammation damages the heart. For these investigations, we have established an experimental model in mice using immunization with cardiac myosin, an important component of heart muscle cells. Lately we have concentrated on the cells that are the most abundant in infiltrates both in human giant cell myocarditis and in our experimental mouse model - macrophages. We have discovered recently that there are different types of macrophages in heart infiltrates and that they can either be disease promoting or—surprisingly—suppressing in myocarditis.

Our preliminary data indicate that the types of macrophages that dominate during the course of myocarditis are influenced by products secreted by infiltrating T cells. Our experiments suggest a product of T cells; IL-17 does not induce proinflammatory functioning macrophages. Since myocarditis in the mouse model is driven by IL-17 cells, this could indicate that IL-17 activated macrophages are not pathogenic in myocarditis but might even be beneficial. A successful mapping of the role of different macrophage subpopulations during myocarditis could have direct implication for novel potential therapies for myocarditis.
Daniela Cihakova, MD, PhD, Johns Hopkins University

“Gene Expression Profiling for Detection of Myocarditis” – December 2007

Over the past 10 years, our group intensified its research in inflammatory heart disease or myocarditis. Myocarditis is estimated to account for about 10-30% of cases with heart failure. Given that heart failure is a severe disease often resulting in poor clinical outcome, early detection of myocarditis becomes extremely important to induce specific treatment that can cure patients. While current diagnostic standards for inflammatory heart disease have insufficient accuracy, our group addresses this issue with a highly sensitive technique, namely gene expression profiling or microarray technology. With this explorative technique, we identified a biomarker, containing 39 genes that distinguish very accurately patients with myocarditis from other types of cardiomyopathy from a single heart biopsy. Besides important improvements in diagnosis of inflammatory heart disease, our findings also offer insight into the pathophysiology of myocarditis on the genetic level and may create the base for new evolving therapies.

Based on our preliminary data, we are currently enrolling patients for a prospective clinical trial, in which we will test the accuracy of our novel biomarker in 150 patients. In order to assure the best possible diagnostic reference to which we will compare our results, state-of-the-art assessment for myocarditis will be combined with novel tools, such as screening for serum antibodies, viral nucleic acids and magnetic resonance imaging. Furthermore, we are seeking to discover markers in corresponding blood cells of our patients, which may allow the use of blood samples as surrogate for heart biopsies. This would be extremely beneficial both for patients and the health care system in terms of time, cost and practicality.
Bettina Heidecker, MD, The University of Miami