Heart failure has become an increasingly prevalent disorder with considerable morbidity and mortality. While many causal mechanisms such as abnormal heart valves, inherited cardiomyopathies, severe coronary artery or hypertensive heart disease are easily identified in clinical practice, the precise mechanisms that determine the progression of heart failure and ventricular remodelling are largely unknown. In recent years, there is growing evidence that autoimmunity and inflammatory mechanisms may contribute to disease progression in heart failure [3, 5, 8, 15]. Viral infections are widely believed to serve as a trigger for initiating autoimmune disease in humans. Sometimes these virus-triggered immune responses progress to a pathogenic autoimmunity state transforming into an autoimmune disease. The pathogenetic process leading from infection to inflammatory dilated cardiomyopathy (DCM) reflects known different stages of an organ-specific autoimmune disease. The first stage is dominated by viral infection itself, the second stage by the onset of multiple autoimmune reactions, and the third stage by the progression to cardiac dilatation and dysfunction [10]. Thus, myocardial inflammation, increased expression of proinflammatory cytokines and circulating autoantibodies are frequently observed in patients with myocarditis and DCM. In animal models an acute myocarditis leading to DCM can be induced both by viral infection or immunization with heart-specific autoantigens such as cardiac myosin or cardiac troponin I [4, 6, 9, 11]. In clinical practice the diagnosis of autoimmune myocarditis requires myocardial biopsy using established histological (Dallas criteria), immunological, and immunohistological criteria or detection of cardiac-reactive autoantibodies in blood. Until now different autoantibodies directed against multiple cardiac antigens have been identified [12]. Circulating autoantibodies may even predict DCM development among relatives of DCM patients years before onset of symptoms [1]. Some antibodies have negative effects not only on myocytes in vitro and in animal models but also in some patients with DCM. In line with these observations is the interesting clinical observation on clinical improvement following extracorporal immunoadsorption of these antibodies [2, 7, 13]. In this issue of Basic Research in Cardiology, Voigt and colleagues report on an enhanced autoimmune response to cardiac proteasomes in DCM patients [14]. They found that proteasome antibody (PA) levels are particularly increased in patients with advanced heart failure. Furthermore, the authors suggested a link between the detection of cardiotropic viruses in endomyocardial biopsies and detection of PA. Likewise, PA levels are enhanced in a murine model of chronic enterovirus myocarditis. Finally they demonstrated that PA exerts negative inotropic effects on cardiomyocytes. The ubiquitin–proteasome system is known to play an important role in regulation of many cellular processes such as expression of transcription factors, regulation of gene transcription, cell proliferation, inflammation, cell death, and the removal of altered or misfolded proteins. Lately, activation or impairment of the ubiquitin–proteasome system has been shown to play a central role in a variety of cardiac diseases [16]. Furthermore there is compelling evidence that degradation-prone substrates accumulate in the myocardium of DCM patients [16]. In this context, the findings of Voigt and colleagues may be important for further understanding of the aetiology of inflammatory cardiovascular diseases and may open new approaches to treatment. Z. Kaya H. A. Katus (&) Department of Cardiology, University of Heidelberg, 69120 Heidelberg, Germany e-mail: sekretariat_katus@med.uni-heidelberg.de