Editorial on the manuscript entitled “Impact of Troponin I-Autoantibodies in Chronic Dilated and Ischemic Cardiomyopathy” by Andreas O. Doesch and co-workers

Abstract

Despite advances in medical treatment, the prognosis of heart failure due to left ventricular systolic dysfunction is poor. In many cases in which disease progression cannot be inhibited by pharmacotherapy, heart transplantation remains the only therapeutic option. The most common causes of heart failure due to myocardial diseases are coronary heart disease, valve diseases, and cardiomyopathies [4]. Dilated cardiomyopathy (DCM) is the third most common cause of heart failure and the most frequent reason for heart transplantation [18]. This myocardial disease is characterized by ventricular chamber enlargement and progressive systolic dysfunction. In approximately 20–35% of DCM cases, a genetic background has been reported [18]. In addition, both experimental and clinical data indicate that viral infection and inflammatory processes may be involved in the pathogenesis of DCM [3, 6, 11, 27]. Abnormalities of the cellular immune system are a common feature of myocarditis and DCM. For patients with DCM, immunohistological methods have been introduced for diagnosis of myocardial inflammation. The term ‘‘inflammatory cardiomyopathy’’ has therefore been coined to describe the etiology of acquired cardiomyopathy [18]. Infiltrations with lymphocytes and mononuclear cells, as well as increased expression of cell adhesion molecules, are frequent phenomena in DCM [14, 21, 26]. These findings support the hypothesis that the immune process is still active. Patients with myocarditis and DCM demonstrate abnormalities of the humoral immune system as well. Furthermore, various autoantibodies have been detected in DCM patients: these include antibodies against mitochondrial proteins [23], cardiac myosin [2], cardiac b1-adrenergic receptors [25], muscarinergic receptors [8], and the sarcolemmal Na-K-ATPase [1]. The functional role of cardiac autoantibodies in DCM is under debate. Antibodies may reflect an inflammatory response to myocyte necrosis, thereby representing an epiphenomenon or, alternatively, may play an active role in the disease process. In patients with chronic myocarditis and cardiomyopathy, the prevalence of antibodies against cardiac myosin is associated with the deterioration of cardiac function [15]. Experimental data indicate that certain cardiac autoantibodies may play a functional role in DCM: antibodies against the ADP/ATP carrier interact with the calcium channel and possess cardiotoxic properties [23]. In the plasma of patients with DCM, negative inotropic antibodies are detectable that decrease the calcium transients of isolated cardiomyocytes [7]. A recent study by Li et al. [17] demonstrated that anti-cardiac myosin antibodies induced by immunization of rats with cardiac myosin target the b-adrenergic receptor on the heart cell surface. Passive transfer of purified antibodies from cardiac myosinimmunized rats results in IgG deposition and apoptosis in the heart, leading to a cardiomyopathic heart disease phenotype in recipients. Immunization of rodents against peptides derived from cardiovascular G-protein receptors induces morphological changes of myocardial tissue resembling DCM [9, 19]. A recent study by Jahns et al. [12] investigated the pathogenic significance of autoantibodies that target cardiac b1-adrenoceptors in DCM: rats immunized against the second extracellular loop of cardiac b1-receptors developed progressive left-ventricular dilatation and dysfunction. Sera transferred from these immunized animals to unsensitized S. B. Felix (&) Klinik fur Innere Medizin B, Ernst-Moritz-Arndt-Universitat Greifswald, Friedrich-Loeffler Str. 23a, 17475 Greifswald, Germany e-mail: felix@uni-greifswald.de