Soluble P2X7 receptor (sP2X7R) as a marker of inflammation in pregnancy

The purinergic P2X7 receptor (P2X7R) is a key regulator of inflammation and pro-inflammatory cytokine release. Recently, a soluble form of P2X7R (sP2X7R) has been identified in the circulation of healthy individuals and significantly increased in patients with inflammatory disorders. As pregnancy is characterized by finely regulated inflammatory adaptations and considered a state of low-grade inflammation, we hypothesized that P2X7R may contribute to the physiological inflammatory status of pregnancy and to pregnancy-related inflammatory disorders. A cohort of 90 pregnant women was evaluated at the first, second, and third trimester of pregnancy, and 30 age-matched non-pregnant women were used as controls. We measured sP2X7R blood concentrations, and the neutrophil-to-lymphocyte ratio (NLR) was used as a reference inflammatory marker. Associations with maternal characteristics, pregnancy complications and foetal sex were investigated. Serum sP2X7R concentrations were significantly higher in pregnant than in control women and increased progressively throughout pregnancy. Although sP2X7R and NLR showed similar trends, sP2X7R provided complementary information. First-trimester sP2X7R concentrations were significantly higher in multigravida women, in those with gestational hypothyroidism, and in those carrying a male foetus. No significant differences were observed according to Body Mass Index (BMI), gestational diabetes, or gestational hypertension. Furthermore, sP2X7R was detectable in umbilical cord blood and positively correlated with maternal circulating concentrations. To our knowledge, this is the first study to show that circulating sP2X7R increases during normal pregnancy and reflects the physiological inflammatory adaptations of gestation. The results indicate that circulating sP2X7R is a potential biomarker of inflammatory responses and maternal-fetal immune interactions during pregnancy.