A serologic marker for fetal risk of congenital heart block

OBJECTIVE: To analyze the humoral immune response to Ro/SSA and La/SSB antigens in detail, in order to identify markers in mothers at high risk of having children with congenital heart block (CHB). METHODS: Serum samples were obtained from 9 Ro/La-positive mothers who gave birth to affected children, from their 8 newborns with CHB, and from 26 Ro/La-positive mothers whose children were healthy. Antibodies against Ro 52-kd, Ro 60-kd, and La were analyzed by enzyme-linked immunosorbent assay and immunoblotting, using recombinant proteins and synthetic peptides. RESULTS: IgG anti-Ro 52-kd antibodies were detected in all mothers who gave birth to children with CHB, as well as in their affected children, but were less frequent and at lower levels in control mothers. Fine mapping revealed a striking difference in which the response in mothers with affected children was dominated by antibodies to amino acids 200-239 of the Ro 52-kd protein (P = 0.0002), whereas the primary activity in control mothers was against amino acids 176-196 (P = 0.001). Furthermore, 8 of 9 mothers of children with CHB had antibody reactivity against amino acids 1-135 of the Ro 52-kd protein, containing 2 putative zinc fingers reconstituted under reducing conditions. CONCLUSION: The results suggest that development of CHB is strongly dependent on a specific antibody profile to Ro 52-kd, which may be a useful tool to identify pregnant Ro/La-positive women at risk of delivering a baby with CHB. Close monitoring of mothers at high risk would enable early detection of a block that is still developing and allow early treatment to combat more serious complications.