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Neonatal lupus: basic research and clinical perspectives
Jill P Buyon1, Robert M Clancy
1Division of Rheumatology, Department of Medicine, New York University School of Medicine, New York, NY, USA. jill.buyon@nyumc.org
Insights
Neonatal lupus can cause severe fetal heart problems, primarily congenital heart block (CHB). Maternal anti-SSA/Ro and anti-SSB/La antibodies are linked to CHB, but fetal factors also play a role.
Area of Science:
- Immunology
- Cardiology
- Neonatology
Background:
- Neonatal lupus (NL) is a rare condition with significant fetal mortality and morbidity, particularly when the heart is affected.
- Congenital heart block (CHB) is a primary cardiac manifestation of NL, occurring in structurally normal hearts.
- Maternal autoantibodies, specifically anti-SSA/Ro and anti-SSB/La, are detected in over 85% of mothers with fetuses diagnosed with CHB.
Purpose of the Study:
- To elucidate the pathogenic mechanisms underlying antibody-mediated cardiac injury in neonatal lupus.
- To explore the spectrum of cardiac abnormalities in fetuses affected by neonatal lupus.
- To identify optimal diagnostic approaches and potential prophylactic strategies for CHB in at-risk pregnancies.
Main Methods:
- Review of in vivo and in vitro evidence detailing the pathological cascade.
- Analysis of echocardiographic findings in fetuses with suspected CHB.
- Examination of the role of maternal autoantibodies and fetal factors in disease development.
Main Results:
- A proposed pathogenic cascade involves cardiocyte apoptosis, antigen translocation, autoantibody binding, and profibrotic factor secretion, leading to a myofibroblast-scarring phenotype.
- The risk of a woman with candidate antibodies having a child with CHB is approximately 2%.
- Cardiac abnormalities range from in utero diagnosed heart block to late-onset cardiomyopathy.
Conclusions:
- Maternal autoantibodies alone are insufficient to cause CHB; fetal factors are likely contributory.
- Early detection of first-degree heart block in utero via echocardiography may be crucial for at-risk pregnancies.
- Prophylactic therapies, such as intravenous immunoglobulin, require further investigation in larger clinical trials.
Abstract:
Neonatal lupus, although quite rare, carries a significant mortality and morbidity when the fetal heart is the targeted organ. Anti-SSA/Ro-SSB/La antibodies are present in more than 85% of mothers whose fetuses are identified with congenital heart block (CHB) in a structurally normal heart, but the risk for a woman who has the candidate antibodies to have a child who has CHB is approximately 2%. Although the precise pathogenic mechanism of injury remains unknown, it is clear that the antibodies alone are insufficient to cause disease, and fetal factors are likely contributory. In vivo and in vitro evidence supports a pathologic cascade, involving apoptosis of cardiocytes, surface translocation of Ro and La antigens, binding of maternal autoantibodies, secretion of profibrosing factors (eg, tumor growth factor ) from the scavenging macrophages, and modulation of cardiac fibroblasts to a myofibroblast-scarring phenotype. The spectrum of cardiac abnormalities encompasses varying degrees of block identified in utero and late-onset cardiomyopathy. Better echocardiographic measurements that identify first-degree block in utero may be the optimal approach for pregnant women at risk; prophylactic therapies, including treatment with intravenous immunoglobulin, await larger trials.