Figure 1.

A two-phase model for the development of congenital heart block. Maternal autoantibodies are transferred to the fetus via the placenta during pregnancy. In a first step, anti-Ro52 antibodies may cross-react to a fetal cardiac molecule involved in calcium regulation and initiate cardiac conduction disturbances, detected as first-degree atrioventricular (AV) block (1). Prolonged disruption of calcium homeostasis may result in increased apoptosis in the fetal heart and subsequent exposure of the Ro and La autoantigens to circulating maternal anti-Ro/La antibodies (2). Engulfment of opsonized apoptotic debris by macrophages (3) may then lead to production of pro-inflammatory and pro-fibrotic cytokines, which, together with antibody deposits and recruitment of complement components, will generate a sustained inflammatory reaction in the fetal heart, eventually leading to permanent damage and complete AV block.