Anti-Beta Adrenergic Receptor Antibody Levels in Pediatric Patients with Biopsy-Proven Myocarditis and Controls

Objectives: Myocarditis can be associated with severe heart failure which may be caused by different inflammatory and autoimmune responses. Anti-β-adrenergic receptor antibodies (anti-β-AR Ab) have been described as elevated in patients with myocarditis and dilated cardiomyopathy leading to heart failure and arrhythmogenic events like Dorner et al and Camino et al have shown. The aim was to analyze anti-β-AR Ab as a marker for the immunological response in children with myocarditis.

Methods: Sera of children hospitalized with biopsy-proven myocarditis were prospectively collected between April 2017 and March 2019. Anti-β1-AR Ab, anti-β2-AR Ab and anti-β3-AR Ab were quantified by a CE-certified ELISA kit. According to normal values for immunoglobulin G (IgG), three age-groups <1 year, 1 to 3 years, and >3 to 17 years were defined. Children without inflammatory cardiac pathology and heart failure served as a control group.

Result: Twenty-two patients with biopsy-proven myocarditis and 28 controls were compared. The median age (IQR) of the myocarditis group was 12.1 (2.7–16.4) years, 13 were male, and left ventricular ejection fraction (LVEF) was 51%. Controls: 5.0 (3.0–6.8) years, 9 males, and LVEF: 64%. Myocarditis patients in the age group >3 to 17 years showed significantly higher anti-β1-AR (cyclic peptide), anti-β2-AR, and anti-β3-AR Ab levels compared with controls (p = 0.011, 0.041, and 0.005, respectively). Lower anti-β2-AR and anti-β3-AR Ab levels were significantly correlated with higher z-score of the left ventricular internal diameter at end diastole (LVIDd; β2: p = 0.029; β3: p = 0.045). Moreover, lower anti-β-1-AR Ab levels (cyclic peptide) were found in children with impaired LVEF (p = 0.049). In patients with levels under the median, the event-free survival of a combined endpoint of mechanical circulatory support, heart transplantation, and/or death was consistently but not significantly lower (40 vs. 80%, p = 0.085).

Conclusion: Anti-β-AR Ab levels are elevated in children with myocarditis and >3 years of age. These Ab might be upregulated compensatory and their role needs to be elucidated with further investigations. Especially children of <3 years with lower Ab levels experience more often adverse events which might be a missing compensatory effect due to lower innate IgG levels.

Publication History

Article published online:
21 February 2021