Feto-Maternal Microchimerism: The Pre-eclampsia Conundrum

Abstract

Feto-maternal microchimerism (FMM) involves bidirectional cross-placental trafficking during pregnancy, leading to a micro-chimeric state that can persist for decades. In this manner a pregnant woman will harbor cells from her mother, as well as, cells from her child. Historically, eclampsia, a severe disorder of pregnancy provided the basis for FMM following the detection of trophoblast cells in the lungs of deceased women. Bi-directional cell trafficking between mother and fetus is also altered in pre-eclampsia and has been suggested to contribute to the underlying etiology. FMM has been implicated in tolerance promotion, remission of auto-inflammatory disorders during pregnancy, or the development of autoimmune conditions post-partum. The underlying mechanism whereby the host immune system is modulated is unclear but appears to involve HLA class II molecules, in that incompatibility between mother and fetus promotes remission of rheumatoid arthritis, whereas feto-maternal HLA compatibility may assist in the post-partum initiation of scleroderma. Couples having a high degree of HLA class II compatibility have an increased risk for pre-eclampsia, while the occurrence of scleroderma and rheumatoid arthritis is greater in pre-eclamptic cases than in women with normal pregnancies, suggesting a long term autoimmune predisposition. Since pregnant women with pre-eclampsia exhibit significantly lower levels of maternally-derived micro-chimerism, the question arises whether pre-eclampsia and post-partum development of autoimmune conditions occur due to the failure of the grandmothers cells to adequately regulate an inappropriate micro-chimeric constellation.

Feto-maternal microchimerism: Memories from pregnancy

“…FMc has been associated with autoimmune tolerance and tissue repair but also with autoimmune diseases and cancer, raising the possibility that they exert multiple and opposing effects in a mother’s body. Also, one should be aware that different pregnancy and birth complications, including preeclampsia, antepartum hemorrhage, and cesarean sections, might alter the functional fate of FMc ( Bianchi et al., 2001 ; Hahn et al., 2019 ; Shree et al., 2019 ). Functionality might also depend on the source tissue, its cellular environment (for instance, pro-vs. anti-inflammatory) and the timepoint analyzed (shortly after delivery, during late postpartum or at a later reproductive age).…”

HLA-G: An Important Mediator of Maternal-Fetal Immune-Tolerance

“…More attention should be given to understanding the role of fetal micro-chimeras in pregnancy. Fetal micro-chimeras are highly associated with maternal autoimmune disease and are found in patients with lower morbidity rates for cancer (154,155). In a study of women with scleroderma, compared to disease-free women, there was reduced sHLA-G expression and higher quantities of persistent fetal micro-chimeras in the circulation (156).…”

Chimerism as the basis for organ repair

“…Interestingly, the presence of male fetal progenitor cells in maternal blood has been reported even at 27 years postpartum 25 . Studies suggest that the kinetics of the trafficking of fetal cells in the mother's blood stream can reveal complications associated with pregnancies, for example, abnormal placentation or conditions such as preeclampsia 26–28 . One of the earliest reports demonstrated the prevalence of male fetal erythroblasts in the maternal circulation in preeclampsia patients, compared with healthy control pregnancies 29 .…”