Abstract
Successful pregnancy requires an immunological shift with T helper CD4+ bias based on disbalance Th1/Th17 versus Th2/T regulatory (Tregs) required to induce tolerance against the semi-allogeneic fetus and placenta and to support fetal growth. Considered a pregnancy-specific hypertensive disorder, pre-eclampsia is characterized by multifaceted organ involvement related to impaired maternal immune tolerance to paternal antigens triggered by hypoxic placental injury as well as excessive local and systemic anti-angiogenic and inflammatory factor synthesis. Both systemic and local Th1/Th2 shift further expands to Th17 cells and their cytokines (IL-17) complemented by suppressive Treg and Th2 cytokines (IL-10, IL-4); alterations in Th17 and Tregs cause hypertension during pregnancy throughout vasoactive factors and endothelial dysfunction, providing an explanatory link between immunological and vascular events in the pathobiology of pre-eclamptic pregnancy. Apart from immunological changes representative of normotensive pregnancy, lupus pregnancy is generally defined by higher serum pro-inflammatory cytokines, lower Th2 polarization, defective and lower number of Tregs, potential blockade of complement inhibitors by anti-phospholipid antibodies, and similar immune alterations to those seen in pre-eclampsia. The current review underpins the immune mechanisms of pre-eclampsia focusing on local (placental) and systemic (maternal) aberrant adaptive and innate immune response versus normotensive pregnancy and pregnancy in systemic autoimmune conditions, particularly lupus.
Highlights
IntroductionPublisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations
Immunologic, angiogenic, and maternal/environmental factors emphasize the complex pathobiology of pre-eclampsia, triggering placental syncytiotrophoblast stress and ischemia associated with immune activation and systemic vascular response [1,2,6–9,15]
Several pathways are proposed to explain the aberrant immunity in Systemic lupus erythematosus (SLE), focusing on the imbalance between production and clearance of apoptotic debris, activated innate and adaptive immunity, inflammatory cell recruitment and tissue injury mediated by the augmented synthesis of pro-inflammatory cytokines derived from activated macrophages (TNFα, IL-6, IL-8), T cells (IL-17) and B cells (IL-10 and IL-6 as a result of IL-21 costimulation), loss of T and B cell tolerance and, excessive autoantibody synthesis partially dependent on a specific type I IFN signature [16–19]
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Immunologic, angiogenic, and maternal/environmental factors emphasize the complex pathobiology of pre-eclampsia, triggering placental syncytiotrophoblast stress and ischemia associated with immune activation and systemic vascular response [1,2,6–9,15]. Impaired maternal immune tolerance to paternal antigens related to hypoxic injury to the placenta is associated with excessive local and systemic anti-angiogenic and inflammatory factor synthesis promoting a serious, life-threatening vascular complication of pregnancy [1,2,6,7,15]. Local (placental) as well as systemic (maternal circulation) immune abnormalities are widely described in the preclinical pre-eclampsia, comprising aberrant excessive complement activation and impaired adaptive T cell tolerance with an imbalance between Th1–Th17 versus Th2–T regs axis shadowed by increased pro-inflammatory (IL-1, IL-6, IL-17, TNF-α) versus decreased anti-inflammatory (IL-4 and IL-10) serum cytokines [1,2,8,10]. The current review emphasizes the immune mechanisms of pre-eclampsia versus normotensive pregnancy and pregnancy in systemic autoimmune rheumatic conditions such as lupus focusing on local (placental) and systemic (maternal) complement, T cell response, and cytokine shift
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