Pregnancy Associated with Systemic Lupus Erythematosus: Immune Tolerance in Pregnancy and Its Deficiency in Systemic Lupus Erythematosus—An Immunological Dilemma

Abstract

Pregnancy is a physiological condition that requires immune tolerance to the product of conception. Systemic lupus erythematosus (SLE) is a disease with well-represented immune mechanisms that disturb immune tolerance. The association of pregnancy with systemic lupus erythematosus creates a particular immune environment in which the immune tolerance specific of pregnancy is required to coexist with alterations of the immune system caused by SLE. The main role is played by T regulatory (Treg) cells, which attempt to regulate and adapt the immune system of the mother to the new conditions of pregnancy. Other components of the immune system also participate to maintain maternal-fetal immune tolerance. If the immune system of pregnant women with SLE is not able to maintain maternal immune tolerance to the fetus, pregnancy complications (miscarriage, fetal hypotrophy, and preterm birth) or maternal complications (preeclampsia or activation of SLE, especially in conditions of lupus nephritis) may occur. In certain situations this can be responsible for neonatal lupus. At the same time, it must be noted that during pregnancy, the immune system is able to achieve immune tolerance while maintaining the anti-infectious immune capacity of the mother. Immunological monitoring of pregnancy during SLE, as well as of the mother's disease, is required. It is important to understand immune tolerance to grafts in transplant pathology.

Pregnancy in systemic lupus erythematosus

“…Recently, Chen et al found a significant increase in the risk of FGR in women with SLE (aOR 2.24, 95% CI [1.85-2.71]; Chen et al, 2020), which is consistent with prior studies (Chakravarty, Nelson, & Krishnan, 2006;Smyth et al, 2010;Wu, Ma, Bao, Di, & Zhang, 2018). Although there are numerous etiologies of FGR, including intrauterine infections, chromosomal anomalies, and multiple gestations, FGR due to placental insufficiency in women with SLE is common (Gluhovschi, Gluhovschi, Petrica, Velciov, & Gluhovschi, 2015). Immune responses have been implicated in the development of placental insufficiency, with complement activation and T-cell signaling playing possible roles (Girardi, Yarilin, Thurman, Holers, & Salmon, 2006;Gluhovschi et al, 2015).…”

“…Although there are numerous etiologies of FGR, including intrauterine infections, chromosomal anomalies, and multiple gestations, FGR due to placental insufficiency in women with SLE is common (Gluhovschi, Gluhovschi, Petrica, Velciov, & Gluhovschi, 2015). Immune responses have been implicated in the development of placental insufficiency, with complement activation and T-cell signaling playing possible roles (Girardi, Yarilin, Thurman, Holers, & Salmon, 2006;Gluhovschi et al, 2015).…”

Pathophysiology and Current Clinical Management of Preeclampsia

“…Over 20% of pregnant women with SLE have pregnancies complicated with PE [59, 60]. For women with lupus nephritis, kidney inflammation due to SLE, who become pregnant, the decrease in Tregs, which are needed for a successful pregnancy puts them at an increased risk for PE [61–64]. SLE is also associated with antiphospholipid antibodies (aPLs) which is associated with PE, preterm birth and intrauterine growth restriction (IUGR) [65, 66].…”

Inactivation of the MAPK signaling pathway by Listeria monocytogenes infection promotes trophoblast giant cell death

“…Pregnancy causes a widely suppression of the adaptive immune system, characterized by a decreased cell-mediated immunity and the suppressed response of cytotoxic T cells ( Gluhovschi et al, 2015 ). Maternal rejection of the fetus is prevented by the immunosuppressed state; however, it has the unexpected effect of increasing maternal susceptibility to abortion-inducing pathogens ( Dhama et al, 2015 ).…”