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.