Table_1_Factors Predicting the Presence of Maternal Cells in Cord Blood and Associated Changes in Immune Cell Composition.pdf

BackgroundCord 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.
Patients and MethodsHere 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.
ResultsMMc 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 (p=0.018) and feto-maternal HLA-A and/or –DR compatibility (p=0.009 and p=0.01 respectively). Finally, CB samples positive for MMc were significantly enriched in CD56+ cells compared to CB negative for MMc.
ConclusionsWe 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.

背景：脐带血（Cord blood, CB）样本在造血干细胞移植领域的应用日益广泛。研究已在脐带血样本中检出母体细胞，且其存在与更优的移植物结局相关。然而，目前尚不明确哪些因素会影响脐带血样本中母体微嵌合（Maternal Microchimerism, MMc）的存在，以及母体细胞是否会对脐带血造血细胞组成产生影响。

患者与方法：本研究针对55名健康初产妇的脐带血样本，探究遗传、生物学、人体测量学及产科相关参数是否会影响脐带血中母体微嵌合的频率与数量。通过靶向非共享、非遗传的人类白细胞抗原（Human Leukocyte Antigen, HLA）特异性实时定量聚合酶链反应，对全血及四种细胞亚群（T淋巴细胞、B淋巴细胞、粒细胞及造血祖细胞）中的母体微嵌合进行检测。此外，本研究通过流式细胞术分析脐带血样本的细胞组成，并依据其微嵌合状态进行分类。

结果：在至少一种细胞亚群或全血中，55%的脐带血样本检出母体微嵌合，其在造血祖细胞中的占比最高可达0.3%。有两项因素可预测脐带血中母体微嵌合的存在：妊娠早期母体血清中妊娠相关蛋白-A的高浓度（p=0.018），以及胎儿-母体HLA-A和/或-DR位点的相容性（分别对应p=0.009与p=0.01）。最终，与母体微嵌合阴性的脐带血样本相比，阳性样本的CD56+细胞占比显著升高。

结论：本研究明确了两项可在妊娠早期检测到的因素，可预测分娩时脐带血样本中母体细胞的存在。同时证实，脐带血中的母体微嵌合可能会影响胎儿细胞的造血组成。CD56是自然杀伤细胞（Natural Killer cells, NK）的表型标记物，而众所周知，自然杀伤细胞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。本研究结果凸显了母体微嵌合检测对于脐带血库构建策略的重要意义。