Abstract 1797: Evidence for Potential Role of Maternal Group A Beta-Hemolytic Streptococcal Infection in Pathogenesis of Hypoplastic Left Heart Syndrome
Background: The etiology of Hypoplastic Left Heart Syndrome (HLHS) is unclear. Our novel hypothesis proposes that HLHS represents a type of rheumatic heart disease in the fetus mediated by transplacental passage of maternal antibodies acquired from prior and recurrent exposure to group A beta-hemolytic streptococci (“strep throat”). This is the first report of our preliminary data.
Methods: One hundred and nine pregnant female patients underwent fetal echocardiography to determine their child’s fetal cardiac status. A detailed maternal history was obtained through a questionnaire tool. Maternal sera from these patients were grouped according to fetal cardiac status and examined for levels of antibodies for DNAse B and Streptolysin O (ASO), and maternal laryngeal and tonsillar cultures were obtained for streptococcal serotyping. Finally, anti-human cardiac myosin (HCM) titers were assessed in HLHS moms as seen in subsets of rheumatic heart disease patients. Myosin peptide studies were carried out to characterize possible anti-HCM responses.
Results: Maternal sera from fourteen patients carrying HLHS babies had significantly elevated anti-DNAse B titers (269.8±342.2; Mean±SD) and anti-ASO (159.3±121.5) titers when compared to 57 healthy pregnant women (106.9±83.3 and 84.6±59.3 IU per mL, respectively). Further analysis of maternal sera demonstrated significantly higher anti-HCM titers (746.2±614.6) in the HLHS group vs. healthy controls (384.6±151.9) with the between group ANOVA and Least Significant Difference post hoc p < 0.01 for all 3 comparisons. Preliminary results indicate that the primary anti-HCM response is against the S2 region of the human cardiac myosin molecule, as seen in patients with rheumatic carditis or cardiomyopathy and myocarditis.
Conclusion: Serologic markers of strep infection were elevated in mothers of infants with HLHS, as well as autoantibodies to human cardiac myosin which are known to be elevated in group A streptococcal sequelae and rheumatic heart disease.