More to death than dying: apoptosis in the pathogenesis of SSA/Ro-SSB/La-associated congenital heart block

The mechanism by which maternal anti-SSA/Ro-SSB/La antibodies initiate and perpetuate inflammation and eventuate in scarring of the atrioventricular node (the signature lesion of congenital heart block) is not yet defined. In vitro and in vivo studies suggest that one pathologic cascade that leads to scarring may be initiated by way of apoptosis which results in translocation of SSA/Ro-SSB/La antigens and subsequent surface binding by maternal autoantibodies. These opsonized cardiocytes are phagocytosed by macrophages, which secrete factors that modulate fibroblasts into myofibroblasts, a scarring phenotype. The exaggerated apoptosis (amplified physiologic apoptosis or defective clearance) that is observed in autopsy slides from fetuses who had congenital heart block may provide the pivotal clue to understanding the pathogenicity of the maternal autoantibodies.