Increased fetal microchimerism in immune and stem cell subsets in preeclampsia.

Abstract

Preeclampsia (PE) is associated with an increased risk of maternal cardiovascular disease (CVD), however, it is unclear whether this is due to shared underlying physiology or changes which occur during the disease process. Fetal microchimerism (FMc) within the maternal circulation can durably persist decades after pregnancy, is known to occur at greater frequency in PE, and can potentially affect local and systemic immune programming, thus changes in cellular FMc may provide a mechanism for long-term health outcomes associated with PE. We investigated whether PE is associated with alterations in FMc immune and stem cell populations. We analyzed maternal peripheral blood mononuclear cells (PBMC) from PE cases (n=16) and matched controls from normal pregnancies (n=16), from which immune and stem cell subsets were isolated by flow cytometry. Genomic DNA was extracted from total PMBC and individual cell subsets, and FMc frequency was quantified by quantitative polymerase chain reaction assays targeting a fetal-specific non-shared polymorphism identified from family genotyping. There was a significant increase in FMc concentration in immune cell subsets in PE cases compared to controls, predominantly in B cell, and NK cell lymphocyte populations. There was no significant difference in FMc frequency or concentration within the stem cell population between PE and controls. The altered concentrations of immune cells within FMc in the maternal blood provides a potential mechanism for the inflammation which occurs during PE to induce long-lasting changes to the maternal immune system and may potentially promote chronic maternal disease.