Feto-Maternal Microchimerism: The Pre-eclampsia Conundrum.

Sinuhe Hahn,Irene Mathilde Hoesli,Lenka Vokalova,Simona W Rossi,Nandor Gabor Than,Olav Lapaire,Shane Vontelin Van Breda,Paul Hasler

doi:10.3389/fimmu.2019.00659

Sinuhe Hahn, Irene Mathilde Hoesli + Show 6 more

Open Access

https://doi.org/10.3389/fimmu.2019.00659

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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.

Highlights

In an examination of maternal blood samples collected from an at-risk cohort we observed an increase in male fetal erythroblasts in samples from cases that subsequently developed pre-eclampsia [35]
A startling finding made during this study was that no evidence of microchimerism due to trafficking maternal cells could be detected in any of the samples obtained from 20 pregnant women with manifest pre-eclampsia, in contrast to matching healthy control pregnant women, where such microchimeric cells could be detected in 30% of cases [60]
Since trans-placental fetal cell traffic is enhanced in cases with pre-eclampsia [34], this would lead to a high level of microchimerism involving HLA class II compatible fetal cells of the type previously observed in cases with systemic sclerosis, autoimmune condition characterized by graft-vs.-host disease-like lesions [21]

Summary

Introduction

In an examination of maternal blood samples collected from an at-risk cohort we observed an increase in male fetal erythroblasts in samples from cases that subsequently developed pre-eclampsia [35]. FMM, can contribute to the subsequent development of an autoimmune condition i.e., rheumatoid arthritis by the provision of necessary HLA haplotypes it via the inheritance of fetal cells or maternal cells during pregnancy [58].

Results

Conclusion