3rd Department of Obstetrics and Gynecology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Department of Obstetrics and Gynecology, "Tzaneio" General Hospital of Piraeus, Piraeus, Greece.
Am J Reprod Immunol. 2019 Mar;81(3):e13087. doi: 10.1111/aji.13087. Epub 2019 Feb 14.
To study the balance of circulating heat shock protein (HSP)60 and HSP70 in pre-term delivery.
A two-stage approach was used. At first stage, we run retrospective analysis of prospective collected clinical data, and at a second stage, we studied an animal model of pre-term delivery (PTD). Blood samples were collected for prenatal screening in 3629 women. Samples from 23 women with miscarriage before gestational week 21 and 53 well-matched comparators for age, body mass index, parity, and previous miscarriage with full-term pregnancy were depicted. Women with risk factors were excluded. HSP60 and HSP70 were measured by an enzyme immunosorbent assay. PTD was induced after injection of low dose of bacterial lipopolysaccharide; mice were killed for the measurement of HSP60 and HSP70 in blood and tissues. The study endpoint was the association of the HSP60 to HSP70 ratio to miscarriage.
A ratio >6 could distinguish between women who will miscarry from women with term pregnancies with sensitivity 60%, specificity 81.8%, positive predictive value 81.8%, and negative predictive value 60% (OR: 6.750, P = 0.025). Mice of the LPS-group PTD had this ratio significantly increased in maternal serum, placentas, and embryos compared to the sham-operation group. Gene expression of hsp60/70 remained in tissues unaltered.
A HSP60/HSP70 ratio equal to or more than 6 until gestational week 12 is accompanied with great likelihood for miscarriage. A similar ratio applies in an animal model of PTD induced by low-dose LPS.
研究早产时循环热休克蛋白（HSP）60 和 HSP70 的平衡。
采用两阶段方法。首先，我们对前瞻性收集的临床数据进行回顾性分析，然后在第二个阶段，我们研究了早产（PTD）的动物模型。对 3629 名妇女进行了产前筛查的血液样本采集。对 23 名在妊娠 21 周前流产的妇女和 53 名年龄、体重指数、产次和有早产史但足月妊娠的匹配对照组进行了回顾性分析。排除有风险因素的妇女。通过酶联免疫吸附试验测定 HSP60 和 HSP70。注射低剂量细菌脂多糖后诱导 PTD；杀死小鼠以测量血液和组织中的 HSP60 和 HSP70。研究终点是 HSP60 与 HSP70 比值与流产的关系。
比值>6 可区分即将流产的妇女和足月妊娠的妇女，其敏感性为 60%，特异性为 81.8%，阳性预测值为 81.8%，阴性预测值为 60%（OR：6.750，P=0.025）。与假手术组相比，LPS 组的 PTD 小鼠母血清、胎盘和胚胎中的该比值显著升高。组织中 hsp60/70 的基因表达不变。
妊娠 12 周前 HSP60/HSP70 比值等于或大于 6 时，流产的可能性很大。在低剂量 LPS 诱导的 PTD 动物模型中也存在类似的比值。
