When the levee doesn't break: A novel role of β2‐glycoprotein I to protect against congenital heart block

Full expression of congenital heart block (CHB), a pathologic readout of autoimmunity in pregnancy with significant morbidity and mortality rates, represents the sum of preclinical intrauterine variables and a morbid triggering event.While exposure to maternal anti-SSA/ Ro and anti-SSB/La antibodies likely represents the trigger of disease, characterization of variables involved in generating a vulnerable fetal heart remains elusive.In this issue of Arthritis & Rheumatism, Reed et al (1) describe a novel interaction between a major candidate target of the maternal immune response in CHB, the 60-kd component of SSA/Ro (Ro 60), and β 2 -glycoprotein I (β 2 GPI), another autoantigen generally thought of in the context of increased thrombophilia (2).This novel interaction generates the hypothesis that a specific biochemical form of Ro 60 may be an important risk variable that is silenced by a putative protective pathway involving β 2 GPI.Review of the molecular structure and function of Ro 60, its translocation to the surface of apoptotic cells, and its subsequent role in physiologic clearance provides the contextual framework for placing an emphasis on β 2 GPI in the pathogenesis of CHB.