Effect of parity on fetal and maternal microchimerism: interaction of grafts within a host?

Abstract

Small amounts of genetically foreign cells (microchimerism, Mc) traffic between a mother and fetus during pregnancy. Commonly, these grafts durably persist. For women, multiple naturally acquired Mc grafts can accrue, as they harbor Mc from their own mothers (maternal Mc, MMc) and subsequently acquire fetal Mc (FMc) through pregnancy. The nature of interactions between these naturally acquired grafts may inform, and be informed by, observations in transplantation, including the effect of noninherited maternal HLA antigens (NIMA) and double-unit cord blood transplantation (CBT). We asked whether FMc and MMc are impacted by the addition of new grafts as evaluated by increasing parity. Mc was identified by quantitative PCR for a nonshared polymorphism unique to the Mc source. Despite increasing sources of Mc, FMc did not increase with increasing parity. MMc concentration was significantly lower with increasing parity. The odds ratio for detection of MMc for 2 or more births compared with 1 birth was .11 (95% CI 0.03-0.42, P = .001). These observations suggest that interactions occur among naturally acquired grafts and are of interest in light of recent observations of graft-graft interaction resulting in predominance of 1 unit in double-unit CBT and the correlation of MMc with the NIMA effect.

Figure 1

Concentration of fetal microchimerism by parity. Scatterplots indicate all values included in the complete analysis. Repeated measures from some subjects are included; linear regression of ranks analysis adjusted for possible correlation between values within a subject via generalized estimating equations. For the comparison between parity of 2-6 compared with 1, also adjusting for age at draw date, P = .42. Below the scatterplot, in tabular form, we have included data reflecting the distribution of fetal Mc quantities detected. For each level of parity, the underlying column indicates the number of samples evaluated, the median concentration of fetal Mc, and the concentrations at the 75th, 90th, and 100th percentiles for the data from all tests at each level of parity.

Figure 2

Concentration of maternal microchimerism by parity. Scatterplots indicate all values included in the complete analysis. Repeated measures from some subjects are included; linear regression of ranks analysis adjusted for possible correlation between values within a subject via generalized estimating equations. For the comparison between parity of 2-4 compared with 1, also adjusting for age at draw date and time from last delivery, P = .02. Below the scatterplot, in tabular form, we have included data reflecting the distribution of maternal Mc quantities detected. For each level of parity, the underlying column indicates the number of samples evaluated, the median concentration of maternal Mc, and the concentrations at the 75th, 90th, and 100th percentiles for the data from all tests at each level of parity.