Robert Hamilton, MD: Autoantibodies Associated with Fetal Cardiac Events

Robert Hamilton, MD, discusses his upcoming ACR presentation, “Fetal Cardiac Targets Identify the Autoantibodies Associated with Congenital Heart Block.” Hamilton and his team hypothesized that maternal antibodies may be characterized based on fetal heart conduction system protein targets.

“In terms of the pathophysiology of the disease, it affects the fetal conduction system, affects the fetal heart rhythm, and blocks the conduction from top to bottom chambers," Hamilton stated. "So, it made sense to us that rather than characterizing maternal autoantibodies based on the typical autoantigens, we should characterize them based on the putative targets.”

Although over 90% of pregnancies that are affected by heart block have moderate to high levels of Ro and La, the reverse isn’t necessarily true. In fact, only 2% of pregnancies that have anti-Ro antibodies ultimately have heart block if no prior pregnancy has been affected.

Investigators used 2-dimensional gels to identify autoantibodies based on target tissue protein.

“We basically take fetal heart tissue, or the other tissue, and we solubilize the proteins from those tissues, separate them in 1 direction on the gel by a characteristic called isoelectric pH, and then separate them in the other direction by molecular weight," Hamilton explained. "That gives you this flat plate of proteins that have been well separated from each other. And then we just transfer those proteins onto a membrane and expose them to serum. The second part is then to confirm to confirm those using commercial proteins using a standard Western and the third part of the method uses a discovery and validation cohort methodology.”

Results indicated that an expanding group of autoantibodies occurred throughout pregnancy, beginning with a single protein around the 7-week mark of gestation and 4 different proteins at 16 to 18 weeks of gestation. Near term, the number of autoantibodies and congenital heart block pregnancies expanded to approximately 30 different autoantibodies to different targets. Additionally, there were about 4 to 7 protein targets that were associated with heart block, 4 of those targets were present before and after heart block occurrence in pregnancy and were solid predictors of heart block.