Male microchimerism in healthy women and women with scleroderma: cells or circulating DNA? A quantitative answer
Male microchimerism in healthy women and women with scleroderma: cells or circulating DNA? A quantitative answer
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DOI：
10.1182/blood-2002-01-0295
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发表时间：
2002-10-15
期刊：
影响因子：
20.3
通讯作者：
Nelson, JL
中科院分区：
文献类型：
--
作者：
Lambert, NC;Lo, YMD;Nelson, JL
男性DNA，假定胎儿起源，可以在分娩后几十年的母体循环中检测到，被称为胎儿微嵌合体（FM）。我们以前发现定量更大的FM在循环中的妇女与自身免疫性疾病硬皮病（SSc）比健康妇女。然而，目前尚不清楚这种差异是由于完整的循环细胞还是受疾病影响的组织中分解释放的游离DNA。为了区分FM的起源，我们开发了一种实时定量聚合酶链反应（PCR）检测Y染色体特异性序列DYS 14，并测试了114名妇女的外周血单核细胞（PBMC）和/或血浆。57名对照和57名SSc患者进行了研究，其中48名和43名分别生下了至少一个儿子。与健康女性（n = 39;范围，0.0-4.4; P = 0.03）相比，SSc患者（n = 39;范围，0.0-12.5男性基因组当量细胞/百万母体细胞）PBMC中的循环FM在数量上更大。相比之下，患者（n = 25）和对照组（n = 22）的血浆中没有差异，也没有游离DNA的证据。对照组（n = 14）的T淋巴细胞与PBMC相比（P = 0.01），FM富集，但SSc患者（n = 14）中没有;后者的发现最有可能是由于免疫抑制药物。总之，这种实时定量分析表明，患有SSc的女性循环中的定量差异是由于细胞而不是游离DNA。由于FM在健康女性中并不罕见，包括在T细胞中，并且由于移植物抗宿主病与SSc具有相似性，因此这些结果也表明FM值得在用于干细胞移植的分离产品中进行研究。
Male DNA, of presumed fetal origin, can be detected in the maternal circulation decades after delivery and is referred to as fetal microchimerism (FM). We previously found quantitatively greater FM in the circulation of women with the autoimmune disease scleroderma (SSc) than of healthy women. However, it is unknown whether this difference is due to intact circulating cells or free DNA released from breakdown in disease-affected tissues. To distinguish the origin of FM, we developed a real-time quantitative polymerase chain reaction (PCR) assay for the Y-chromosome-specific sequence DYS14, and tested 114 women in peripheral blood mononuclear cells (PBMCs) and/or plasma. Fifty-seven controls and 57 SSc patients were studied, 48 and 43 of whom, respectively, had given birth to at least one son. Circulating FM was quantitatively greater in PBMCs from SSc patients (n = 39; range, 0.0-12.5 male genome-equivalent cells per million maternal cells), compared with healthy women (n = 39; range, 0.0-4.4; P = .03). In contrast, there was no difference between patients (n = 25) and controls (n = 22) in plasma, and no evidence of free DNA. FM was enriched among T lymphocytes compared with PBMCs (P = .01) in controls (n = 14), but not in SSc patients (n = 14); the latter finding was most likely due to immunosuppressive medications. In conclusion, this real-time quantitative assay showed that quantitative differences in the circulation of women with SSc are due to cells and not to free DNA. As FM was not uncommon in healthy women, including among T cells, and because graft-versus-host disease has similarities to SSc, these results also suggest that FM merits investigation in pheresis products used for stem cell transplantation.