New biomarkers for autoimmune congenital heart block identified

Ana-Luisa Stefanski and colleagues from the group of Thomas Dörner, DRFZ and Charité – Universitätsmedizin Berlin, in cooperation with the Department of Obstetrics at Charité, have identified new biomarkers and potential causes of autoimmune congenital heart block (CHB). In CHB, the heartbeat of the unborn child significantly slows down, which can result in death of the foetus. This complication occurs in expectant mothers with anti-SSA antibodies, which can occur in Sjögren’s disease, systemic lupus erythematosus, but also in some pregnant women without any symptoms. The results have now been published in the journal Annals of the Rheumatic Diseases.

The causes of this rare complication have not been sufficiently investigated, which limits therapeutic interventions. However, it is known that anti-SSA antibodies from the mother enter the foetus via the placenta. These antibodies are directed against protein molecules of cell nuclei and can also attack the heart cells of the foetus.

Approximately 2-3% of babies born to anti-SSA-positive mothers develop CHB. Biomarkers are needed to better identify CHB risk pregnancies. Stefanski et al. found that anti-SSA-positive mothers of CHB-affected children had significantly higher circulating levels of the soluble molecules sPD-L1, sCD86 and s4-1BB in their blood during pregnancy compared to anti-SSA-A-positive pregnant women without complications and healthy pregnant women. In addition, high-risk pregnancies with an increased type I interferon signature could be distinguished from CHB by high sPD-L1 and sCD86 levels.

The molecule PD-L1 is usually expressed on the trophoblast cells, specific cells of the placenta, and plays a role in the development of immunological tolerance during pregnancy. PD-L1 is important to prevent the foetus from being rejected by the mother’s immune system. Trophoblast cells from CHB placentas have less PD-L1 on the cell surface than healthy placentas. The researchers are now investigating what this means and to what extent therapeutic intervention in this dysregulation offers possibilities for protection against CHB.