Dissecting the pathogenic mechanism in congenital heart block

Many autoimmune conditions are associated with an increased risk of pregnancy complications and fetal loss.

Sjögren’s syndrome and SLE are rheumatic autoimmune conditions in which autoantibodies to the SSA and SSB antigens are commonly found. During pregnancy, the maternal autoantibodies are transported across the placenta and affect the developing child. This may lead to a neonatal lupus syndrome, including a congenital heart block with high lethality.

This project aims at specifying key steps in the pathogenesis, and using our world-uniqe cohorts and biobanks together with animal models and in vitro systems we will define fetal susceptibility genes and identify the fetal cardiac target bound by the heart-block inducing antibodies, and use these discoveries to delineate the mechanism by which the maternal autoantibodies induce the inflammatory environment and heart block in the expected child.

Our strategic setup enables us to move from the clinical problem to cellular and molecular understanding of the disease and back to the patient.

The data obtained from the studies will be important for understanding of how fetal immune-mediated disease develops, and will have wider implications for other inflammatory conditions.

Importantly, the results will contribute towards identifying targets and strategies suitable for novel preventive measures, diagnostics and treatment of human immune-mediated disease with specific implications for congenital heart block.