Obstetrics: Pore-forming proteins - implication for the pathology of HELLP syndrome

Pregnant women with pre-eclampsia have an increased risk of developing HELLP syndrome, which is a condition characterised by Haemolysis, Elevated Liver enzymes and Low Platelet count. HELLP complicates 0.2-0,8% of all pregnancies. There is currently no treatment for the syndrome and acute delivery has to be provoked to save mother and child. HELLP is considered to be an inappropriate immune reaction to the pregnancy involving the complement system. The compliment system normally facilitates eradication of bacteria. However, under certain pathological circumstances, it can attack our own cells and cause damage. We have shown that in human erythrocytes, membrane insertion of MAC resulted in release of ATP. Scavenging of this ATP or blockage of P2X-receptors completely prevented complement-induced haemolysis, whereas addition of additional ATP potentiates the haemolysis. Moreover ATP and its degradation product ADP are potent stimulators of thrombocyte aggregation and thus, MAC-induced ATP release would potentially reduce the total platelet number, as seen in HELLP syndrome. It is therefore highly likely that compliment induced release of ATP and activation of P2-receptors occurs early in the development of HELLP syndrome.
The hypothesis is that we can avoid some of the cell damage that occurs in HELLP syndrome by blocking ATP-receptors.