16:00-16:10 Detection of microchimeric fetal cells in maternal peripheral blood during and after oocyte donation pregnancy

K. van Bentem, M. van den Nagel,J.J.M. Drabbels, E.E.L.O. Lashley,M. Eikmans,M.L.P. van der Hoorn

Journal of Reproductive Immunology(2023)

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摘要
Since fetal microchimerism (FMc) has been associated with both beneficial and harmful effects on maternal health, it is a topic of interest in current investigations. Oocyte donation (OD) pregnancies serve as an interesting model to investigate the maternal immune system and the immunological events associated with pregnancy, including the presence of FMc. OD pregnancies are characterized by a higher degree of fetal-maternal immunogenetic dissimilarity compared to autologous pregnancies. Consequently, the maternal immune system is expected to adapt more in order to maintain a successful pregnancy. Herein, the relevance of FMc after OD pregnancy remains unclear. Therefore, the aim of this study was to detect and quantify fetal microchimeric cells in maternal blood after OD pregnancy, and to relate this to the extent of fetal-maternal human leukocyte antigen (HLA) mismatching. Maternal peripheral blood samples obtained during OD pregnancy with a male fetus (n = 16, whole blood, ranging from first to third trimester), six weeks after OD pregnancy (n = 16, mononuclear cells), and directly after autologous pregnancy with a male fetus (n = 15, whole blood) were analysed for the presence of male FMc using quantitative polymerase chain reaction (qPCR) for a Y-chromosome-specific sequence (DYS1). In addition, umbilical cord blood samples were collected directly after delivery. Maternal and fetal HLA typing was performed at split level for HLA class I loci A, B, and C and for HLA class II loci DR1 and DQ1 to calculate the number of fetal-maternal HLA mismatches. Male FMc was detected in 14 of 16 (87.5%) women during OD pregnancy, 12 of 16 (75.0%) women at six weeks after OD pregnancy, and 14 of 15 (93.3%) women after autologous pregnancy. The median genome equivalent values for these three groups were 1.368 (0 – 11.947), 1.301 (0 – 9.371), and 4.107 (0 – 26.941), respectively (p = not significant between groups). When the number of fetal-maternal HLA mismatches of the autologous group and postpartum OD group were taken into account, the amount of FMc was significantly lower after pregnancies with high immunogenetic dissimilarity (6-10 total HLA mismatches) compared to low immunogenetic dissimilarity (0-5 total HLA mismatches; p = 0.039). When the number of fetal-maternal HLA mismatches of only the postpartum OD group were taken into account, the amount of FMc was also lowest in high immunogenetic pregnancies (4-6 mismatches for HLA class I, 3-4 mismatches for HLA class II, 6-10 for total HLA mismatches), though without statistical significance. FMc is detectable in maternal blood after OD pregnancy, and a higher degree of fetal-maternal immunogenetic dissimilarity may be related to decreased amounts of FMc. Due to the limited sample size, the study is further expanded to establish a conclusive analysis of the association between the amount of FMc and the number of fetal-maternal HLA mismatching. Nonetheless, this is the first study to investigate this association, which might provide new insights of the maternal immune response and its interaction
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关键词
microchimeric fetal cells,maternal peripheral blood,pregnancy
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