INSERM UMRs 1097 Arthrites Autoimmunes, Aix Marseille Université, Marseille, France.
Department of Obstetrics and Gynecology, St Joseph Hospital, Marseille, France.
Front Immunol. 2021 Apr 22;12:651399. doi: 10.3389/fimmu.2021.651399. eCollection 2021.
Cord blood (CB) samples are increasingly used as a source of hematopoietic stem cells in transplantation settings. Maternal cells have been detected in CB samples and their presence is associated with a better graft outcome. However, we still do not know what influences the presence of maternal microchimerism (MMc) in CB samples and whether their presence influences CB hematopoietic cell composition.
Here we test whether genetic, biological, anthropometric and/or obstetrical parameters influence the frequency and/or quantity of maternal Mc in CB samples from 55 healthy primigravid women. Mc was evaluated by targeting non-shared, non-inherited Human Leukocyte Antigen (HLA)-specific real-time quantitative PCR in whole blood and four cell subsets (T, B lymphocytes, granulocytes and/or hematopoietic progenitor cells). Furthermore CB samples were analyzed for their cell composition by flow cytometry and categorized according to their microchimeric status.
MMc was present in 55% of CB samples in at least one cell subset or whole blood, with levels reaching up to 0.3% of hematopoietic progenitor cells. Two factors were predictive of the presence of MMc in CB samples: high concentrations of maternal serological Pregnancy-Associated-Protein-A at first trimester of pregnancy () and feto-maternal HLA-A and/or -DR compatibility ( and respectively). Finally, CB samples positive for MMc were significantly enriched in CD56+ cells compared to CB negative for MMc.
We have identified two factors, measurable at early pregnancy, predicting the presence of maternal cells in CB samples at delivery. We have shown that MMc in CB samples could have an influence on the hematopoietic composition of fetal cells. CD56 is the phenotypic marker of natural killer cells (NK) and NK cells are known to be the main effector for graft versus leukemia reactions early after hematopoietic stem cell transplantation. These results emphasize the importance of MMc investigation for CB banking strategies.
脐带血(CB)样本越来越多地被用作移植环境中造血干细胞的来源。已经在 CB 样本中检测到母体细胞,其存在与更好的移植物结果相关。然而,我们仍然不知道是什么影响 CB 样本中母体微嵌合体(MMc)的存在,以及它们的存在是否影响 CB 造血细胞组成。
在这里,我们测试了遗传、生物学、人体测量学和/或产科参数是否影响 55 名健康初产妇 CB 样本中母体 Mc 的频率和/或数量。通过针对非共享、非遗传的人类白细胞抗原(HLA)特异性实时定量 PCR 在全血和四个细胞亚群(T、B 淋巴细胞、粒细胞和/或造血祖细胞)中评估 Mc。此外,通过流式细胞术分析 CB 样本的细胞组成,并根据其微嵌合状态进行分类。
MMc 存在于 55%的 CB 样本中的至少一个细胞亚群或全血中,水平高达造血祖细胞的 0.3%。有两个因素可以预测 CB 样本中 MMc 的存在:妊娠早期母体血清妊娠相关蛋白-A 浓度高()和胎母 HLA-A 和/或 -DR 相容性(和分别)。最后,与 MMc 阴性的 CB 样本相比,MMc 阳性的 CB 样本显著富含 CD56+细胞。
我们已经确定了两个因素,它们可以在妊娠早期测量,预测分娩时 CB 样本中母体细胞的存在。我们表明,CB 样本中的 MMc 可能对胎儿细胞的造血组成有影响。CD56 是自然杀伤细胞(NK)的表型标志物,NK 细胞已知是造血干细胞移植后早期移植物抗白血病反应的主要效应细胞。这些结果强调了对 CB 储存策略进行 MMc 研究的重要性。