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早发型子痫前期患者治疗性血浆置换后 sB7-H4 血清水平和胎盘生物标志物表达的改变。

Alteration in sB7-H4 Serum Levels and Placental Biomarker Expression after Therapeutic Plasma Exchange in Early-Onset Preeclampsia Patients.

机构信息

Department of Gynecology and Obstetrics, University of Duisburg-Essen, 45147 Essen, Germany.

Department of Nephrology, University of Duisburg-Essen, University Hospital Essen, 45147 Essen, Germany.

出版信息

Int J Mol Sci. 2024 Oct 15;25(20):11082. doi: 10.3390/ijms252011082.

Abstract

Therapeutic plasma exchange (TPE) is a widely used treatment for numerous diseases including pregnancy-related conditions. Our prior study on 20 early-onset preeclampsia patients undergoing TPE revealed a significant extension in pregnancy duration and reduced serum levels of sFlt-1, sFlt-1/PlGF, and sEndoglin. Here, we investigated the impact of TPE on serum sB7-H4, an immunological checkpoint molecule, and placental proteins (Flt-1, Eng, B7-H4, iNOS, TNF-α) in TPE-treated early-onset preeclampsia patients (N = 12, 23 + 2-28 + 5 weeks), conventionally treated counterparts (N = 12, 23 + 5-30 weeks), and gestational age-matched controls (N = 8, 22 + 4-31 + 6 weeks). Immunoblotting, ELISA, and co-immunohistochemistry were used for biomarker analysis, including placental inflammation factors (iNOS, TNF-α). The results showed that TPE extended pregnancy by a median of 6.5 days in this cohort of early-onset preeclampsia. Serum sB7-H4, sFlt-1, and sEndoglin levels decreased, along with reduced expression of their membrane-bound proteins in placental tissue upon TPE treatment. Moreover, TPE-treated patients displayed reduced placental inflammation compared to preeclampsia patients receiving standard-of-care treatment. In conclusion, TPE may improve pregnancy outcomes in early-onset preeclampsia by lowering circulating levels of sB7-H4, sFlt-1, and sEndoglin, as well as reducing placental inflammation. This translational approach holds promise for enhancing placental function and extending gestation in high-risk pregnancies including very preterm PE or HELLP cases.

摘要

治疗性血浆置换(TPE)是一种广泛应用于治疗多种疾病的方法,包括与妊娠相关的疾病。我们之前对 20 例早发型子痫前期患者进行 TPE 的研究表明,TPE 可显著延长妊娠时间,并降低血清可溶性 fms 样酪氨酸激酶-1(sFlt-1)、sFlt-1/胎盘生长因子(PlGF)和可溶性内皮糖蛋白(sEndoglin)水平。在此,我们研究了 TPE 对 TPE 治疗的早发型子痫前期患者(N = 12,23+2-28+5 周)、常规治疗对照组(N = 12,23+5-30 周)和胎龄匹配对照组(N = 8,22+4-31+6 周)血清 sB7-H4(一种免疫检查点分子)和胎盘蛋白(Flt-1、Eng、B7-H4、诱导型一氧化氮合酶(iNOS)、肿瘤坏死因子-α(TNF-α))的影响。采用免疫印迹、ELISA 和共免疫组织化学方法分析生物标志物,包括胎盘炎症因子(iNOS、TNF-α)。结果显示,在该早发型子痫前期队列中,TPE 将妊娠平均延长了 6.5 天。TPE 治疗后,血清 sB7-H4、sFlt-1 和 sEndoglin 水平降低,胎盘组织中其膜结合蛋白的表达减少。此外,与接受标准治疗的子痫前期患者相比,TPE 治疗患者的胎盘炎症减轻。综上所述,TPE 通过降低循环中 sB7-H4、sFlt-1 和 sEndoglin 的水平以及减轻胎盘炎症,可能改善早发型子痫前期的妊娠结局。这种转化方法有望增强高危妊娠(包括极早产 PE 或 HELLP 病例)的胎盘功能并延长妊娠时间。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62af/11507903/110b6108ea97/ijms-25-11082-g001.jpg

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