Cardiac Autoimmunity: Myocarditis

Abstract

Myocarditis is the inflammation of the muscle tissues of the heart (myocardium). After a pathologic cardiac-specific inflammatory process, it may progress to chronic damage and dilated cardiomyopathy. The latter is characterized by systolic dysfunction, whose clinical correlate is heart failure. Nevertheless, other acute complications may arise as consequence of tissue damage and electrophysiologic disturbances. Different etiologies are involved in triggering myocarditis. In some cases, such as giant cell myocarditis or eosinophilic necrotizing myocarditis, it is an autoimmune process. Several factors predispose the development of autoimmune myocarditis such as systemic/local primary autoimmunity, viral infection, HLA and gender bias, exposure of cryptic antigens, mimicry, and deficient thymic training/Treg induction. Once the anti-myocardium autoimmune process is triggered, several components of the immune response orchestrate a sustained attack toward myocardial tissues with particular timing and immunopathogenic features. Innate response mediated by monocytes/macrophages, neutrophils, and eosinophils parallels the adaptive response, playing a final effector role and not only a priming function. Stromal cells like fibroblast are also involved in the process through specific cytokines. Furthermore, adaptive T cell responses have anti-paradigmatic features, as Th17 response is dispensable for acute myocarditis but is the main driver of the process leading to dilated cardiomyopathy. Humoral response, thought to be a bystander, is important in the appearance of late-stage hemodynamic complications. The complexity of that process, as well as the unspecific and variable clinical presentation, had generated difficulties for diagnosis and treatment, which remain suboptimal. In this chapter, we will discuss the most relevant immunopathogenic findings from a basic science and clinical perspective.

Keywords: Adaptive response; Autoimmunity; Dilated cardiomyopathy; Myocarditis.

Fig. 10.1

Proposed model for myocarditis development. Coexistence of predisposing factors along with specific triggers of myocardium damage leads to exposure of cryptic self-antigens and a consequent inflammatory process. At this point, both the innate and the myocardium-specific adaptive response generate a self-sustained autoimmune phenomenon independent of the original trigger factor. That autoimmune process is responsible for development of myocarditis and progression to DCM

Fig. 10.2

Schematic immunopathogenesis of post-myocarditis DCM development. CD4 T cell autoimmune response induces a Th17-dependent pro-inflammatory process associated with DCM development. T cell-derived IL17A induces cardiac fibroblasts to produce GM-CSF, which in turns activates monocytes toward a highly inflammatory function. Those activated monocytes are required final effectors in the progression to chronic tissue damage and DCM