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A serologic marker for fetal risk of congenital heart block
Stina Salomonsson1, Thomas Dörner, Elke Theander
1Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
Insights
Specific antibodies to the Ro 52-kd protein, particularly to amino acids 200-239, can identify mothers at high risk for congenital heart block (CHB). This finding aids in early detection and potential treatment for affected newborns.
Area of Science:
- Immunology
- Maternal-Fetal Medicine
- Pediatric Cardiology
Background:
- Congenital heart block (CHB) is a serious complication of maternal autoantibodies.
- Ro/SSA and La/SSB autoantibodies are associated with CHB, but specific predictive markers are needed.
- Understanding the humoral immune response to Ro/SSA and La/SSB antigens is crucial for risk stratification.
Purpose of the Study:
- To precisely analyze the maternal humoral immune response to Ro/SSA and La/SSB antigens.
- To identify specific antibody profiles that predict the risk of CHB in offspring.
- To establish markers for early identification of high-risk pregnancies.
Main Methods:
- Serum samples were collected from mothers with CHB-affected children (n=9) and control mothers with healthy children (n=26).
- Antibodies against Ro 52-kd, Ro 60-kd, and La antigens were quantified using enzyme-linked immunosorbent assay and immunoblotting.
- Recombinant proteins and synthetic peptides were employed for fine mapping of antibody epitopes.
Main Results:
- All mothers of CHB-affected children had IgG anti-Ro 52-kd antibodies, with higher frequency and levels compared to controls.
- A significant difference was observed in antibody targets: mothers of affected children primarily targeted amino acids 200-239 of Ro 52-kd.
- Antibody reactivity against amino acids 1-135 of Ro 52-kd, containing zinc fingers, was present in 8 of 9 mothers of CHB-affected infants.
Conclusions:
- A specific antibody profile against Ro 52-kd is strongly associated with CHB development.
- This antibody profile can serve as a valuable tool for identifying pregnant women at risk for delivering a baby with CHB.
- Early detection and monitoring of high-risk pregnancies can facilitate timely intervention and management of CHB.
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.