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The possibility that cardiac autoimmunity contributes to the pathogenesis of Chagas heart disease is controversial. In this paper, we address the following questions regarding the genesis of autoimmunity in Chagas heart disease: (i) What mechanism(s) are potentially responsible for the generation of self-directed antibodies and lymphocytes? (ii) What is the evidence that any of these mechanisms actually can occur? (iii) What are the implications of the presence of autoimmunity for other mechanisms of cardiac inflammation?