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Disruption of the Mouse Blood-Brain Barrier by Small Extracellular Vesicles from Hypoxic Human Placentas

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Immunology of pre-eclampsia.

Christopher W G Redman¹, Ian L Sargent

¹Nuffield Department of Obstetrics and Gynaecology, University of Oxford, John Radcliffe Hospital, Oxford, UK. christopher.redman@obs-gyn.ox.ac.uk

American Journal of Reproductive Immunology (New York, N.Y. : 1989)

|March 25, 2010

Summary

Pre-eclampsia stems from placental oxidative stress, not fetal antigens. Maternal immune adaptation to paternal antigens is key to preventing this pregnancy disorder.

Area of Science:

Reproductive immunology
Maternal-fetal medicine
Pathogenesis of pre-eclampsia

Background:

Pre-eclampsia is a multi-stage condition, with the clinical illness representing the final stage.
The systemic inflammatory response in pre-eclampsia is secondary to placental oxidative stress, not fetal alloantigen reactivity.
Maternal adaptation to paternal alloantigens is critical in earlier, pre-clinical stages of pregnancy.

Purpose of the Study:

To elucidate the immune mechanisms underlying pre-eclampsia pathogenesis.
To explain the first pregnancy preponderance and partner specificity observed in pre-eclampsia.
To link the development of pre-eclampsia to defined immune processes at the fetomaternal interface.

Main Methods:

Review and synthesis of existing immunological and clinical data on pre-eclampsia.

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Hypothesizing immune pathways involving seminal plasma tolerization, regulatory T cells, indoleamine 2,3-dioxygenase, and NK cell recognition.

Analysis of the role of HLA-C on extravillous trophoblast in placental development and immunoregulation.

Main Results:

Maternal tolerization to paternal antigens via seminal plasma is proposed for the pre-conceptual phase.
Regulatory T cells and indoleamine 2,3-dioxygenase, along with decidual NK cell recognition of fetal HLA-C, may facilitate placental growth.
Partial failure of these immune mechanisms can lead to poor placentation and uteroplacental dysfunction, explaining pre-eclampsia.

Conclusions:

Pre-eclampsia pathogenesis is linked to specific immune mechanisms at the fetomaternal frontier.
The model explains pre-eclampsia's association with first pregnancies and specific partners.
Further research is needed to validate these proposed immune pathways in detail.