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移植前终末期肾病女性外周血单个核细胞中高水平的男性微嵌合体。

Male microchimerism at high levels in peripheral blood mononuclear cells from women with end stage renal disease before kidney transplantation.

机构信息

UMC Transplantation Rénale, Hôpital Pasteur, Centre Hospitalo-Universitaire de Nice, Nice, France.

出版信息

PLoS One. 2012;7(3):e32248. doi: 10.1371/journal.pone.0032248. Epub 2012 Mar 5.

Abstract

Patients with end stage renal diseases (ESRD) are generally tested for donor chimerism after kidney transplantation for tolerance mechanism purposes. But, to our knowledge, no data are available on natural and/or iatrogenic microchimerism (Mc), deriving from pregnancy and/or blood transfusion, acquired prior to transplantation. In this context, we tested the prevalence of male Mc using a real time PCR assay for DYS14, a Y-chromosome specific sequence, in peripheral blood mononuclear cells (PBMC) from 55 women with ESRD, prior to their first kidney transplantation, and compared them with results from 82 healthy women. Male Mc was also quantified in 5 native kidney biopsies obtained two to four years prior to blood testing and in PBMC from 8 women collected after female kidney transplantation, several years after the initial blood testing. Women with ESRD showed statistically higher frequencies (62%) and quantities (98 genome equivalent cells per million of host cells, gEq/M) of male Mc in their PBMC than healthy women (16% and 0.3 gEq/M, p<0.00001 and p = 0.0005 respectively). Male Mc was increased in women with ESRD whether they had or not a history of male pregnancy and/or of blood transfusion. Three out of five renal biopsies obtained a few years prior to the blood test also contained Mc, but no correlation could be established between earlier Mc in a kidney and later presence in PBMC. Finally, several years after female kidney transplantation, male Mc was totally cleared from PBMC in all women tested but one. This intriguing and striking initial result of natural and iatrogenic male Mc persistence in peripheral blood from women with ESRD raises several hypotheses for the possible role of these cells in renal diseases. Further studies are needed to elucidate mechanisms of recruitment and persistence of Mc in women with ESRD.

摘要

患有终末期肾病(ESRD)的患者通常会在肾移植后接受供体嵌合检测,以了解其耐受机制。但据我们所知,目前尚无关于自然和/或医源性微嵌合体(Mc)的数据,这些 Mc 源自于妊娠和/或输血,发生在移植之前。在此背景下,我们使用实时 PCR 检测外周血单个核细胞(PBMC)中的 Y 染色体特异性序列 DYS14,来检测 55 名 ESRD 女性在首次肾移植前的男性 Mc 患病率,并与 82 名健康女性的结果进行比较。我们还在 5 份肾活检组织中检测了 2 到 4 年前采集的、以及 8 名女性在最初血液检测多年后接受女性肾移植后采集的 PBMC 中的男性 Mc 量。与健康女性相比,ESRD 女性的 PBMC 中男性 Mc 的频率(62%)和数量(98 个基因组当量细胞/百万宿主细胞,gEq/M)更高(分别为 62%和 98 个基因组当量细胞/百万宿主细胞,p<0.00001 和 p = 0.0005)。无论 ESRD 女性是否有男性妊娠和/或输血史,其男性 Mc 均增加。在血液检测前几年采集的 5 份肾活检组织中也有 Mc,但未能确定早期肾活检中的 Mc 与后期 PBMC 中的 Mc 之间的相关性。最后,在所有接受检测的女性中,女性肾移植多年后,其 PBMC 中的男性 Mc 完全清除,除了 1 名女性。这一令人惊讶的初步结果表明,患有 ESRD 的女性外周血中存在自然和医源性的男性 Mc 持续存在,这引发了关于这些细胞在肾脏疾病中可能作用的几个假设。需要进一步研究来阐明 ESRD 女性中 Mc 的募集和持续存在的机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cc9/3293902/88ba9c6f5a33/pone.0032248.g001.jpg

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