Specificity and effector mechanisms of autoantibodies in congenital heart block

Complete congenital atrio-ventricular (AV) heart block develops in 2–5% of fetuses of Ro/SSA and La/SSB autoantibody-positive pregnant women. During pregnancy, the Ro/SSA and La/SSB antibodies are transported across the placenta and affect the fetus. Emerging data suggest that this happens by a two-stage process. In the first step, maternal autoantibodies bind fetal cardiomyocytes, dysregulate calcium homestasis and induce apoptosis in affected cells. This step might clinically correspond to a first-degree heart block, and be reversible. La/SSB antibodies can bind apoptotic cardiomyocytes and thus increase Ig deposition in the heart. The tissue damage could, as a second step, lead to spread of inflammation in genetically pre-disposed fetuses, progressing to fibrosis and calcification of the AV-node and subsequent complete congenital heart block. Early intrauterine treatment of an incomplete AV-block with fluorinated steroids has been shown to prevent progression of the heart block, making it clinically important to find specific markers to identify the high-risk pregnancies.