Immunology of Preeclampsia

Abstract

Preeclampsia is a placenta-dependent disorder with both local and systemic anomalies with neonatal and maternal morbidity. It is manifested late in pregnancy, but the onset is during early stages of gestation. The current hypothesis regarding the aetiology of preeclampsia is focused on maladaptation of immune responses and defective trophoblast invasion. Thus, an excessive maternal inflammatory response, perhaps directed against foreign fetal antigens, results in a chain of events including shallow trophoblast invasion, defective spiral artery remodelling, placental infarction and release of pro-inflammatory cytokines and placental fragments in the systemic circulation. During normal pregnancy, trophoblasts interact in the decidua with the unique uterine NK cells, modifying their cytokine repertoire, regulating adhesion molecules and matrix metalloproteinases. The inability of trophoblasts to accomplish these changes might be a critical factor for the onset of preeclampsia. Several cytokines, produced at the maternal-fetal interface, have an impact on trophoblast invasion. It is suggested that deficiency of interleukin-10 may contribute to enhanced inflammatory responses towards the trophoblasts elicited by e.g. tumour necrosis factor-alpha and interferon-gamma. Consequently, trophoblasts subjected to a high rate of apoptosis are hampered in their invasive capacity resulting in defective transformation of spiral arteries, hypoxia, thrombosis and infarction of the placenta. The ensuing infarction of placenta leads to leakage of increasing amounts of placental fragments and cytokines in the maternal circulation and an exaggerated systemic endothelial activation as identified in preeclampsia. So far, treatment of preeclampsia is focused on signs like hypertension, whereas attempts of modifying immune responses may be a possibility in the future.

Acute kidney injury in pregnancy: a clinical challenge

“…Both trigger endothelial dysfunction and severe preeclampsia (34,35). The placental ischemia, reperfusion and associated oxidative stress amplify apoptosis by rupture of syncytial architecture and promote the release into the maternal circulation of several components (syncytiotrophoblast membrane microparticles and an excess of antiangiogenic factors, such as sFlt-1) that stimulate the synthesis of inflammatory cytokines (36)(37)(38). This excessive inflammatory response causes endothelial dysfunction, increased vascular reactivity and coagulopathy that precede the development of symptomatic disease (39).…”

Involvement of membrane GRP78 in trophoblastic cell fusion

“…In PE, incomplete differentiation of CTBs to both invasive and villous CTBs was observed. As a consequence, there is shallow invasion of the pregnant uterus and defective syncytin expression in STB responsible for the characterized disturbances in STB in PE such as increased numbers of syncytial knots [31] [26].…”

The role of tumor necrosis factor-receptors in pregnancy with normal and adverse outcome

“…147 Peripheral blood mononuclear cells and decidual lymphocytes express higher levels of Th1 cytokines, including TNFα, and lower Th2 cytokine expression in preeclampsia compared to normal pregnancy. 148,149 This is reflected in the maternal circulation, with a further rise in pro-inflammatory cytokines such as TNFα, accompanied by an elevated level of soluble receptor in an attempt to dampen the cytokine response. [150][151][152][153] Increased levels of TNFα and other pro-inflammatory cytokines have also been found in the umbilical serum of pregnancies complicated by preeclampsia, suggesting a role in intra-uterine growth restriction secondary to preeclampsia.…”