Autoimmunity Against the Heart and Cardiac Myosin in Children With Myocarditis

• Levels of antibodies to cardiac myosin in children with clinical myocarditis were higher than in control children.
• Neither antibody levels at initial presentation or at follow-up corresponded to recovery of normal cardiac function according to echocardiography.
• Antibody-mediated activation of protein kinase A was higher at presentation in children with myocarditis who did not recover by 12 months after diagnosis.
• Differences in antibody-mediated cell signaling, rather than just antibody levels, may play a role in cellular damage and possibly outcomes in children with myocarditis.

BackgroundHost autoimmune activity in myocarditis has been proposed to play a role in development of cardiac disease, but evidence of autoimmunity and relationship to outcomes have not been evaluated in pediatric myocarditis.MethodsWe performed a multi-institutional study of children with clinical myocarditis. Newly diagnosed patients were followed for up to 12 months and previously diagnosed patients at a single follow-up for serum levels of autoantibodies to human cardiac myosin, beta-adrenergic receptors 1 and 2, muscarinic-2 receptors, and antibody-mediated protein kinase A (PKA) activation in heart cells in culture. Results were compared with those of healthy control children.ResultsBoth previously diagnosed patient at follow-up (P = .0061) and newly diagnosed patients at presentation (P = .0127) had elevated cardiac myosin antibodies compared with control subjects. Antibody levels were not associated with recovery status at follow-up in either group. PKA activation was higher at presentation in the newly diagnosed patients who did not recovery normal function (P = .042).ConclusionsChildren with myocarditis have evidence of autoantibodies against human cardiac myosin at diagnosis and follow-up compared with control subjects. Differences in antibody-mediated cell signaling may contribute to differences in patient outcomes, as suggested by elevated antibody-mediated PKA activation in heart cells by the serum from nonrecovered patients.