Effect of Maternal Autoantibodies on Fetal Cardiac Conduction: An Experimental Murine Model

Abstract

The pathogenesis of congenital heart block (CHB) remains unclear. The occurrence rate of neonatal CHB is low, even in murine models of lupus erythematosus. The assessment of heart block in murine maternal lupus models by measuring atrioventricular conduction in neonatal offspring is potentially confounded by fetal wastage. We therefore sought to develop a murine CHB model with a superior immune response and to use embryonic Doppler echocardiography to observe conduction system damage in the fetus. Mature 8-wk-old female C3H/HeJ mice (n=43) were immunized with 60 kD Ro, 48 kD La, or recombinant calreticulin autoantigens. ELISA confirmed that significant serum autoantibodies developed in all three immunized groups when compared with controls. Starting at 13 d of gestation, a significantly lower fetal heart rate (HR) and a higher percentage of fetal bradycardia/atrioventricular block (AVB, nonadvanced second degree) were observed in all immunized groups, compared with controls. There was 9-18% nonadvanced second-degree AVB in immunized groups and 0% in controls at <18 d of gestation. Neonatal electrocardiograms demonstrated only 1 degrees AVB in immunized groups. Maternal immunization with 60 kD Ro, 48 kD La, or recombinant calreticulin autoantigens resulted in AVB in a significant percentage of fetuses, however, lesser degrees of AVB were seen at birth. Significant fetal bradycardia and AVB may be missed by assessment only at birth in murine models of CHB due to fetal wastage.