CD19+CD5+ Cells as Indicators of Preeclampsia
CD19+CD5+ Cells as Indicators of Preeclampsia
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DOI：
10.1161/hypertensionaha.111.188276
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发表时间：
2012-04-01
期刊：
影响因子：
8.3
通讯作者：
Zenclussen, Ana Claudia
中科院分区：
文献类型：
--
作者：
Jensen, Federico;Wallukat, Gerd;Zenclussen, Ana Claudia
先兆子痫是一种破坏性的妊娠相关疾病，全世界5%至8%的孕妇受到影响。它作为一种自身免疫驱动的疾病出现，其中，抗血管紧张素1型受体II的自身抗体被认为是先兆子痫症状的原因。尽管很多注意力集中在描述与先兆子痫相关的自身抗体上，但没有关于产生这些抗体的细胞群体的线索。CD19(+)CD5(+)B-1aB细胞是天然抗体和多反应抗体的主要来源，可针对自身结构产生抗体。在这里，我们的目标是确定在子痫前期期间负责自身抗体产生的B细胞亚群，并研究它们的调节，以及它们作为疾病标志物的可能用途。用流式细胞仪分析，子痫前期患者外周血中CD19(+)CD5(+)细胞的频率明显高于正常孕妇。这似乎是由于与正常孕妇相比，子痫前期患者血清和胎盘上清液中存在较高的人类绒毛膜促性腺激素水平。大约95%的CD19(+)CD5(+)细胞表达人绒毛膜促性腺激素受体，而且这些细胞在淋巴细胞培养中也在人绒毛膜促性腺激素的刺激下扩增。最重要的是，分离的CD19(+)CD5(+)细胞产生抗血管紧张素1型受体II的自身抗体，CD19(+)CD5(+)细胞在先兆子痫患者的胎盘中进一步检测到，但在正常妊娠中几乎不存在B细胞。我们的结果发现，能够产生妊娠病理性自身抗体的B细胞群体可能是先兆子痫的标志，这打开了广泛的诊断和治疗应用。(高血压。2012年；59：861-868。)。在线数据补充
Preeclampsia is a devastating pregnancy-associated disorder affecting 5% to 8% of pregnant women worldwide. It emerges as an autoimmune-driven disease, and, among others, the autoantibodies against angiotensin type 1 receptor II have been proposed to account for preeclampsia symptoms. Despite much attention focused on describing autoantibodies associated with preeclampsia, there is no clue concerning the cell population producing them. CD19(+) CD5(+) B-1a B cells constitute the main source of natural and polyreactive antibodies, which can be directed against own structures. Here, we aimed to identify the B-cell subpopulation responsible for autoantibody production during preeclampsia and to study their regulation, as well as their possible use as markers for the disease. The frequency of CD19(+)CD5(+) cells in peripheral blood of preeclamptic patients is dramatically increased compared with normal pregnant women as analyzed by flow cytometry. This seems to be driven by the high human chorionic gonadotropin levels present in the serum and placenta supernatant of preeclamptic patients versus normal pregnant women. Not only approximate to 95% of CD19(+)CD5(+) cells express the human chorionic gonadotropin receptor, but these cells also expand on human chorionic gonadotropin stimulation in a lymphocyte culture. Most importantly, isolated CD19(+)CD5(+) cells produce autoantibodies against angiotensin type 1 receptor II, and CD19(+)CD5(+) cells were further detected in the placenta of preeclamptic but not of normal pregnancies where barely B cells are present. Our results identify a B-cell population able to produce pregnancy-pathological autoantibodies as possible markers for preeclampsia, which opens vast diagnostic and therapeutic applications. (Hypertension. 2012;59:861-868.). Online Data Supplement