Elevated Levels of Total Cell-Free DNA in Maternal Serum Samples Arise from the Generation of Neutrophil Extracellular Traps
Elevated Levels of Total Cell-Free DNA in Maternal Serum Samples Arise from the Generation of Neutrophil Extracellular Traps
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DOI：
10.1159/000444853
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发表时间：
2016-01-01
影响因子：
2.2
通讯作者：
Giaglis, Stavros
中科院分区：
文献类型：
--
作者：
Chowdhury, Chanchal Sur;Hahn, Sinuhe;Giaglis, Stavros
母体血液样本的无细胞DNA分析促进了胎儿非整倍体或遗传性孟德尔疾病的无创检测。在此背景下，先前的研究表明，母体血清中的游离DNA比血浆样本中的游离DNA更多，因此需要优化收集和储存方案。由于游离DNA数量增加的来源尚不清楚，我们现在研究了中性粒细胞胞外陷阱（NETs）是否有助于这种物质。材料与方法：采集正常健康孕妇妊娠三个月及有明显子痫前期的足月血清样本。通过检测与中性粒细胞颗粒蛋白（即髓过氧化物酶）络合的无细胞DNA片段，证实了net衍生物质的存在。结果：我们的数据表明，net来源的无细胞DNA/髓过氧化物酶复合物在正常孕妇的血清中高于正常配对的非孕妇对照。这种中性粒细胞染色体物质在整个妊娠期间逐渐增加，在先兆子痫的病例中最为明显。讨论：通过检测母体血清样本中游离DNA/髓过氧化物酶复合物水平的增加，我们的数据表明，这种物质的很大一部分来自NETs的产生。(C) 2016 S. Karger AG，巴塞尔
Introduction: The analysis of cell-free DNA from maternal blood samples has facilitated the noninvasive detection of fetal aneuploidies or hereditary Mendelian disorders. In this context, previous studies have indicated that the pool of cell-free DNA is greater in maternal serum than in plasma samples, necessitating optimized collection and storage protocols. As the source of this increased amount of cell-free DNA is not clear, we have now examined whether neutrophil extracellular traps (NETs) contribute to this material. Material and Methods: Serum samples were collected in all three trimesters of normal healthy pregnant women, and at term from cases with manifest preeclampsia. The presence of NET-derived material was demonstrated by the detection of cell-free DNA fragments complexed to neutrophil granular proteins (i.e. myeloperoxidase). Results: Our data indicate that NET-derived cell-free DNA/myeloperoxidase complexes were greater in serum from normal pregnant women than in normal matching nonpregnant controls. This neutrophil chromosomal material increased incrementally throughout gestation and was most pronounced in cases with pre-eclampsia. Discussion: By detecting increased levels of cell-free DNA/myeloperoxidase complexes in maternal serum samples, our data indicate that a significant proportion of this material is derived from the generation of NETs. (C) 2016 S. Karger AG, Basel