Dilated Cardiomyopathy and The Role of Autoimmunity in...

An autoimmune response directed against heart-specific antigens has been recognized as important to the pathogenesis of DCM. Specifically, muscarinic M2AChR autoantibodies have a 25-80% occurrence in various cardiac conditions; these antibodies can be found in 18-51% of patients with idiopathic DCM (4), 40-77% of chagasic patients with heart failure and 42% of those with an unspecified condition (18, 31). A wide variety of infectious and noninfectious agents have been reported to induce similar symptoms (32, 33), and recently, a cancer patient undergoing chemotherapy with cisplatin and doxorubicin showed a DCM phenotype and the concomitant presence of serum autoantibodies against M2AChR (6). It is well established that cardiomyopathy can be recapitulated by experimental immunization with cardiac myosin plus an adjuvant or with the administration of antibodies against troponin I and the ÃŽ ²1-adrenergic receptor (33, 28, 34, 35). Similarly, we provide evidence that autoimmunity again st specific M2AChR epitopes (M2AChR-el2 and M2AChR-il3) may play a causal role in DCM. Therefore, BALB/c mice were DNA-immunized using a gene gun with plasmids encoding partial epitopes to induce potentially harmful anti-M2AChR-el2 and anti-M2AChR-il3 antibodies and establish cardiomyopathy. All mice progressively developed left ventricle dilation and dysfunction detected by echocardiography analyses (approximately 10-20 weeks post-immunization). Next, we mimicked the presence of autoantibodies