**7. Acknowledgements**

396 Myocarditis

understand whether –and if so, then to which extent– the specific target of a heart-directed autoantibody, but also its respective titre and biological activity and –last not least– its respective kinetics (that is, antibody-persistence or -clearance over time) relate to the complex process of cardiac wounding and healing. Different cardiac aabs might have distinct propensities to induce a certain cardiac phenotype, and the ETiCS study will allow for a differentiation of such features in a prospective manner. Thereby, additional prognostic markers for patients with an unfavourable course of autoimmune heart failure might be recognised and, as a consequence, conventional treatment modalities could be optimized earlier and/or novel -more specific- treatment strategies could be developed.

Despite available treatment guidelines, the recent progress in conventional pharmacotherapy, and promising novel device-based therapeutic approaches, the outcome of patients suffering from heart failure remains unsatisfactory. This has stimulated the search for causal treatment strategies aiming to block or neutralize factors thought to play a

In a large number of neurologic, rheumatologic, and endocrine disorders autoimmune phenomena have been recognised as main disease-causing factors. Their relevance in human heart disease and failure, however, still need to be substantiated (Jahns et al., 2006; Fu, M., 2008) although preliminary clinical data suggest that the presence of certain cardiac aabs clearly worsens the prognosis of patients with idiopathic DCM (Störk et al., 2006). Therapeutic strategies known from other autoimmune disorders, such as application of peptide-ligands (for multiple sclerosis (Warren et al., 2006)) or immunoadsorption of disease-causing aabs (for myasthenia gravis (Tzartos et al., 2008)) might thus also offer

In this regard, recent *in vitro* experiments with functionally active receptor-aabs isolated from a smaller number of DCM-patients indicate, that aab-induced adrenoceptor activation might be abrogated by incubation with epitope-mimicking peptides (Nikolaev et al., 2007; Jahns et al. 2010). Although clinical *in vivo* data with epitope-derived antibody-scavengers are still lacking, the latter *in vitro* findings together with the results from the ETiCS study should stimulate further research in the field of specifically antibody-directed therapeutic

In addition to established anti-adrenergic drugs like cardioselective beta-blockers such strategies might comprise (a) the aforementioned epitope-derived peptides as antibodyscavengers (Jahns et al., 2010), (b) an elimination of functionally active cardiac aabs by selective or non-selective immunoadsorption (studies currently under way (Felix & Staudt, 2008; Müller et al., 2008)), or (c) the direct targeting/suppression of autoantibody-producing

At least in animal models of antibody-induced immune-cardiomyopathy and –nephropathy some of these novel therapeutic approaches have already been successfully applied (Jahns et al., 2005; Matsui et al., 2006; Neubert et al., 2008; Jahns et al., 2010). Hence, the results from the clinical (diagnostic) ETiCS study might also furnish a basis for and accelerate further pre-clinical development of such novel therapeutic approaches and agents targeting at cardio-noxious aabs, and –hopefully– for a faster transfer into clinical practice. Moreover, by initiating a joint venture of the leading European research institutes in the field of cardiac autoimmunity, ETiCS could equally serve as a starting point for future common efforts to

**6. Future perspectives and therapeutic implications** 

treatment options for a variety of human cardiac disorders.

B cells and/or plasma-cells themselves (Neubert et al., 2008).

role in heart failure progression.

strategies.

The investigator-initiated ETiCS study receives public funding from the German Ministry for Education and Research (Bundesministerium für Bildung und Forschung, BMBF Project number 01ES0816). The ETiCS study has been acknowledged by the German Competence Network Heart Failure (CNHF, subproject 6b), and has equally been associated to the BMBF-funded Comprehensive Heart Failure Centre, University Hospital of Würzburg (CHFC, associated project C4). All authors had full access to the data and have read and approved the final article and have declared no conflicts of interest.
