Maternal autoantibodies directed to the p200 epitope of Ro52 correlate with fetal AV block and directly bind cardiomyocytes, dysregulating calcium homeostasis and inducing apoptosis.
Congenital heart block develops in fetuses after placental transfer of Ro/SSA autoantibodies from rheumatic mothers. The condition is often fatal and the majority of live-born children require a pacemaker at an early age. The specific antibody that induces the heart block and the mechanism by which it mediates the pathogenic effect have not been elucidated. In this study, we define the cellular mechanism leading to the disease and show that maternal autoantibodies directed to a specific epitope within the leucine zipper amino acid sequence 200-239 (p200) of the Ro52 protein correlate with prolongation of fetal atrioventricular (AV) time and heart block. This finding was further confirmed experimentally in that pups born to rats immunized with p200 peptide developed AV block. p200-specific autoantibodies cloned from patients bound cultured cardiomyocytes and severely affected Ca2+ oscillations, leading to accumulating levels and overload of intracellular Ca2+ levels with subsequent loss of contractility and ultimately apoptosis. These findings suggest that passive transfer of maternal p200 autoantibodies causes congenital heart block by dysregulating Ca2+ homeostasis and inducing death in affected cells.
Salomonsson et al. (Mon,) conducted a other in Congenital heart block. Maternal autoantibodies directed to p200 of Ro52 protein was evaluated on Prolongation of fetal atrioventricular (AV) time and heart block, and cellular Ca2+ dysregulation. Maternal autoantibodies directed to the p200 epitope of Ro52 correlate with fetal AV block and directly bind cardiomyocytes, dysregulating calcium homeostasis and inducing apoptosis.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: