Molecular pathology of inflammatory cardiomyopathy

Abstract

Endomyocardial biopsy (EMB) is often performed in patients presenting with sudden onset of heart failure to identify myocarditis. The introduction of immunohistochemical techniques for the detection and differentiation of infiltrating immune cells, specific adhesion molecules and MHC class I and II molecules increased the prognostic value of EMB in the diagnosis of myocarditis considerably. A major breakthrough in the understanding of pathogenetic mechanisms in myocarditis was achieved by diagnostic use of molecular biological methods. By application of in situ hybridization and PCR, enteroviruses, and more recently, parvovirus B19 (PVB19) have been identified as relevant agents of myocarditis. The different cell tropism of these viruses implicates distinct pathogenic principles, which, at present, are not completely understood. Whereas enteroviruses damage the heart primarily via direct lysis of infected myocytes, PVB19 does not infect myocytes, but endothelial cells of small intracardiac arterioles and venules, resulting in impairment of myocardial microcirculation with secondary myocyte necrosis during acute infection. Histological and immunohistological stainings combined with molecular biological approaches in EMB will help us to resolve the question of whether patients with myocarditis should be treated by specific antiviral agents or by immunosuppressive therapies.

The prevalence of enteroviral capsid protein vp1 immunostaining in pancreatic islets in human type 1 diabetes

“…However, in common with others [19,23] we also noted that the Dako antiserum can, under certain conditions, label tissues in which vp1 production is not expected. In particular, our preliminary work revealed that, when applied to formalin-fixed, paraffin-embedded sections of Coxsackie-infected neonatal mouse organs, this antibody stained some tissues which were reported to be negative for viral RNA by in situ hybridisation [24].…”

High Prevalence of Cardiac Parvovirus B19 Infection in Patients With Isolated Left Ventricular Diastolic Dysfunction

“…6 Endothelial cells have been recognized as targets for PVB19 infection in small cardiac vessels, whereas cardiomyocytes have so far not been described as targets for this virus type. 9,23,24 The most likely cardiac location of PVB19 in our patient is the endothelium, based on all currently available studies in humans. 9,23,24 Alternatively, PVB19 could also reside in other cardiac cell types or in blood-borne cells, which previously might have migrated into the heart.…”

“…9,23,24 The most likely cardiac location of PVB19 in our patient is the endothelium, based on all currently available studies in humans. 9,23,24 Alternatively, PVB19 could also reside in other cardiac cell types or in blood-borne cells, which previously might have migrated into the heart. However, at the time of investigation, no circulating cells carrying PVB19 were detected in any patient.…”

Identification of HLA-A*01- and HLA-A*02-restricted CD8+ T-cell epitopes shared among group B enteroviruses

“…The relevance of the CD8 + T cells for an efficient elimination of CVB3 during the acute phase of myocarditis was demonstrated in the mouse model of enterovirus myocarditis (Klingel et al, 2003). Moreover, the severity of CVB3 myocarditis was found to be magnified in CD8 2/2 mice (Opavsky et al, 1999), suggesting a dominant role of CD8 + T cells in the protection against enterovirus challenge.…”