PP13, Maternal ABO Blood Groups and the Risk Assessment of Pregnancy Complications

Abstract

BackgroundPlacental Protein 13 (PP13), an early biomarker of preeclampsia, is a placenta-specific galectin that binds beta-galactosides, building-blocks of ABO blood-group antigens, possibly affecting its bioavailability in blood.Methods and FindingsWe studied PP13-binding to erythrocytes, maternal blood-group effect on serum PP13 and its performance as a predictor of preeclampsia and intrauterine growth restriction (IUGR). Datasets of maternal serum PP13 in Caucasian (n = 1078) and Hispanic (n = 242) women were analyzed according to blood groups. In vivo, in vitro and in silico PP13-binding to ABO blood-group antigens and erythrocytes were studied by PP13-immunostainings of placental tissue-microarrays, flow-cytometry of erythrocyte-bound PP13, and model-building of PP13 - blood-group H antigen complex, respectively. Women with blood group AB had the lowest serum PP13 in the first trimester, while those with blood group B had the highest PP13 throughout pregnancy. In accordance, PP13-binding was the strongest to blood-group AB erythrocytes and weakest to blood-group B erythrocytes. PP13-staining of maternal and fetal erythrocytes was revealed, and a plausible molecular model of PP13 complexed with blood-group H antigen was built. Adjustment of PP13 MoMs to maternal ABO blood group improved the prediction accuracy of first trimester maternal serum PP13 MoMs for preeclampsia and IUGR.ConclusionsABO blood group can alter PP13-bioavailability in blood, and it may also be a key determinant for other lectins' bioavailability in the circulation. The adjustment of PP13 MoMs to ABO blood group improves the predictive accuracy of this test.

The relationship between maternal blood group and preeclampsia

“…8 The results of our study are consistent with findings of Lee BK et al 9 Bharali et al 10 Spinillo et al 11 C Phaloprakram et al 12 One suggested mechanism of how blood group influences the risk of gestational hypertensive disorders is through the maternal immune response. Placental Protein 13 (PP13) is considered to be an early marker for preeclampsia.…”

“…PP13 is primarily produced by the placenta in anthropoid primates It is a galectin (galectin-13) that binds betagalactosides, such as N-acetyl-galactosamine, galactose, fucose, located at terminal positions on ABO blood-group antigens, with strongest affinity to blood group AB. 8 In women from AB group, the close proximity of A and B antigens could explain the stronger binding of PP13 to blood group AB erythrocytes, leading to its sequestration. In consequence the PP13 plasma levels are low in pregnant on the first trimester of gestation, which could predispose pregnancy complications, including preeclampsia.…”

“…Low plasma concentrations of these glycoproteins in blood-group O individuals may lead to excess bleeding, while elevated plasma concentrations of these factors in non-O bloodgroup individuals have been implicated in increasing the risk of thromboembolic and ischemic heart diseases. 8 Recent genome-wide association studies indicate that genetic variants at the ABO locus are associated with soluble E-selectin, 17,18 P-selectin, and ICAM-1, 19 vascular inflammatory agents that are associated with hypertension and type-2 diabetes. 20 However, of a diverse panel of inflammatorybiomarkers, including Eselectin, P-selectin, and ICAM-1, a recentstudy found that only E-selectin levels were higher in preeclampsiacases versus controls.…”

“…It is a key determinant of coagulation factor VIII and von Willebrand factor plasma concentrations. 8 ABO antigens may alter the presentation of cell-surface glycans and modulate their interactions with pathogens or may provide receptors for pathogen attachment, hence ABO antigen is associated with various diseases. ABO antigens may play a major role in the interaction of the immune and coagulation systems by influencing geneenvironment interactions.…”

Effects of Placental Protein 13 on the Cardiovascular System in Gravid and Non-Gravid Rodents

“…PP13 was identified to bind to red blood cells, particularly those that carry the blood groups AB and B, which represent the majority of the population [25]. Thus, there is an abundance of PP13 that is released from the syncytiotrophoblast into maternal blood, and a significant amount is bound to red blood cells circulating in maternal blood vessels, adding to the significant PP13 levels in maternal serum.…”