Dynamic Changes in Fetal Microchimerism in Maternal Peripheral Blood Mononuclear Cells, CD4+ and CD8+ cells in Normal Pregnancy

Abstract

Objective Cell trafficking during pregnancy results in persistence of small populations of fetal cells in the mother, known as fetal microchimerism (FMc). Changes in cell-free fetal DNA during gestation have been well-described, however, less is known about dynamic changes in fetal immune cells in maternal blood. We investigated FMc in maternal peripheral blood mononuclear cells (PBMC) longitudinally across gestation. Study Design Thirty-five women with normal pregnancies were studied. FMc was identified in PBMC, CD4+ and CD8+ subsets employing quantitative PCR assays targeting fetal-specific genetic polymorphisms. FMc quantities were reported as fetal genome equivalents (gEq) per 1,000,000 gEq mother’s cells. Poisson regression modeled the rate of FMc detection. Main Outcome Measure FMc in PBMC Results The probability of detecting one fetal cell equivalent increased 6.2-fold each trimester [Incidence Rate Ratio (IRR) 95% CI: 1.73, 21.91; p=0.005]. Although FMC in PBMC was not detected for the majority of time points, 7 of 35 women had detectable FMc during pregnancy at one or more time points, with the majority of positive samples being from the third trimester. There was a suggestion of greater HLA-sharing in families where women had FMc in PBMC. FMc was detected in 9% of CD4+ (2/23) and 18% of CD8+ (3/25) subsets. Conclusions FMc in PBMC increased as gestation progressed and was found within CD4+ and CD8+ subsets in some women in the latter half of gestation. A number of factors could influence cellular FMc levels including subclinical fetal-maternal interface changes and events related to parturition. Whether FMc during pregnancy predicts persistent FMc and/or correlates with fetal-maternal HLA-relationships also merits further study.

The Number of Endovascular Trophoblasts in Maternal Blood Increases Overnight and after Physical Activity: An Experimental Study

“…1, 2, 3). However, cytokine levels, HLA sharing, and fetal gender may be of importance [12,16]. Differences in placenta sizes have been previously studied but do not seem to be a factor at early gestational ages [12].…”

Naturally acquired microchimerism

“…Human fetal or maternal microchimeric cells can be found in circulating blood cells such as granulocytes, 51 lymphocytes, 52 monocytes, 53 and myeloid dendritic cells 54,55 as well as in organs and tissues 56 Using quantitative PCR technology for the detection of nonshared polymorphic HLA genes unique to mother-and fetus-derived cells, it was shown that adult women often carry multiple types of naturally acquired chimeric cells derived from different sources, i.e., from their mother and from their offspring. Addressing the prevalence of these two types of chimeric cells specifically within short-lived and continuously replenished cells of myeloid origin, Nelson and colleagues demonstrated that maternal microchimerism is actually more common in granulocytes obtained from adult females than fetal microchimerism.…”

Microchimérisme fœtal : soi et non soi, finalement qui sommes-nous ?

“…Le passage transplacentaire des cellules foetales débute très tôt au cours de la grossesse [32] et se prolonge pendant toute la grossesse pour être à son maximum dans les derniers mois de grossesse [33].…”

“…Chez la femme, le microchimérisme est plus fréquent lorsqu'elle présente une compatibilité HLA soit avec le père, soit avec sa propre mère. L'influence de la compatibilité avec sa mère s'expliquerait par l'acquisition de cellules maternelles (microchimérisme maternel) durant sa propre vie foetale [33]. Le génotype HLA de la source de microchimérisme peut également influencer la présence ou non de ces cellules microchimériques.…”