Relationship between maternal immunological response during pregnancy and onset of preeclampsia

Abstract

Maternofetal immune tolerance is essential to maintain pregnancy. The maternal immunological tolerance to the semiallogeneic fetus becomes greater in egg donation pregnancies with unrelated donors as the complete fetal genome is allogeneic to the mother. Instead of being rejected, the allogeneic fetus is tolerated by the pregnant woman in egg donation pregnancies. It has been reported that maternal morbidity during egg donation pregnancies is higher as compared with spontaneous or in vitro fertilization pregnancies. Particularly, egg donation pregnancies are associated with a higher incidence of pregnancy-induced hypertension and placental pathology. Preeclampsia, a pregnancy-specific disease characterized by the development of both hypertension and proteinuria, remains the leading cause of maternal and perinatal mortality and morbidity. The aim of this review is to characterize and relate the maternofetal immunological tolerance phenomenon during pregnancies with a semiallogenic fetus, which are the spontaneously conceived pregnancies and in vitro fertilization pregnancies, and those with an allogeneic fetus or egg donation pregnancies. Maternofetal immune tolerance in uncomplicated pregnancies and pathological pregnancies, such as those with preeclampsia, has also been assessed. Moreover, whether an inadequate maternal immunological response to the allogenic fetus could lead to a higher prevalence of preeclampsia in egg donation pregnancies has been addressed.

Figure 1

Maternofetal immune response in preeclampsia. A series of events occurs in the maternal-fetal interface in preeclampsia that result in an altered expression of different factors (PIGF, sENG, sFLT1, GM-CSF, and TLR-4) as compared to normal pregnancies. Similarly, the ratio among various populations of immune cells (Th17/Treg, Th1/Th2) differs from normality in preeclamptic patients. Regarding the complement system, preeclampsia enhances MBL and C5a synthesis. These changes are evidenced in peripheral blood in which the proinflammatory systemic environment is also seen with high IL-6 a, TNF-alpha, IL-8, IP-10, MCP-1, ICAM-1, and VCAM-1 levels. Treg: CD4+CD25+Foxp3+ T regulatory cells; TLR: toll-like receptor; HLA: the human leukocyte antigen; uNk cell: uterine natural killer cell; KIR: killer immunoglobulin-like receptor; sFLT1: soluble fms-like tyrosine kinase-1 factor; sENG: soluble endoglin; PIGF: placenta growth factor; GM-CSF: granulocyte-macrophage colony-stimulating factor; MBL: mannose-binding lectin; Th cell: T helper cell; IL: interleukin; IFNg: interferon gamma; TNF-alpha: tumor necrosis factor alpha; IP-10: interferon-inducible-protein-10; MCP-1: monocyte chemotactic protein-1; ICAM-1: intercellular adhesion molecule 1; VCAM-1: vascular cell adhesion protein 1; Th17: a subpopulation of TCD4+ effector cells, Thelper 17 cells.