PP125. High mobility group box 1 protein (HMGB1): A pathogenic role in preeclampsia?

A central pathogenic mechanism of preeclampsia is believed to be the production by the hypoxic placenta of various mediators which promote inflammation and oxidative stress when released into the maternal circulation. The high mobility group box 1 protein (HMGB1) is a ubiquitous nuclear protein. In conditions of hypoxic cellular stress or necrosis, HMGB1 is released into the extracellular milieu. Extracellular HMGB1 has proinflammatory effects, due to the engagement of various cell membrane receptors, notably the receptor for advanced glycation products (RAGE).

In preeclampsia, there is evidence for activation of RAGE, and enhanced amounts of HMGB1 have also been demonstrated in the placenta and amniotic fluid, but not, so far, in maternal blood. We hypothesize therefore that, in preeclampsia, the concentration of HMGB1 is abnormally high in maternal blood.

We enrolled 16 women in third trimester pregnancy and suffering from preeclampsia (blood pressure > 140/90mmHg with significant proteinuria), 16 women with normal pregnancies who were matched pairwise with the former for BMI and gestation week, and 16 non pregnant healthy women, matched for age with the other two groups. HMGB1 was assessed in peripheral blood with a commercial ELISA kit. The variance between the three groups was appreciated using an ANOVA analysis. Significance was considered for a probability value of < 0.5.

The median [interquartile range] HMGB1 concentrations (in ng/mL) were 2.1 [1.1-3.2] in preeclamptic pregnancies, 1.1 [1.0-1.2] in normal pregnancies (p<0.05 vs preeclamptic group), and 0.6 [0.5-0.8] in non pregnant women (p<0.01 vs both other groups).

In third trimester pregnancy, the presence of preeclampsia is associated with an approximately two-fold increase of HMGB1 concentration in maternal peripheral blood. Considering its known proinflammatory effects, HMGB1 could be one mediator responsible for the maternal manifestations of preeclampsia.