Department of Pathology, University of California, San Diego, La Jolla, CA, USA; Center for Perinatal Discovery, University of California, San Diego, La Jolla, CA, USA.
Department of Pathology, University of California, San Diego, La Jolla, CA, USA; Center for Perinatal Discovery, University of California, San Diego, La Jolla, CA, USA; Sanford Consortium for Regenerative Medicine, University of California, San Diego, La Jolla, CA, USA.
Placenta. 2023 Dec;144:13-22. doi: 10.1016/j.placenta.2023.10.008. Epub 2023 Oct 20.
Mortality from preeclampsia (PE) and PE-associated morbidities are 3-to 5-fold higher in persons of African ancestry than in those of Asian and European ancestries.
To elucidate placental contribution to worse PE outcomes in African ancestry pregnancies, we performed bulk RNA sequencing on 50 placentas from persons with severe PE (sPE) of African (n = 9), Asian (n = 18) and European (n = 23) ancestries and 73 normotensive controls of African (n = 10), Asian (n = 15) and European (n = 48) ancestries.
Previously described canonical preeclampsia genes, involved in metabolism and hypoxia/angiogenesis including: LEP, HK2, FSTL3, FLT1, ENG, TMEM45A, ARHGEF4 and HTRA1 were upregulated sPE versus normotensive placentas across ancestries. LTF, NPR3 and PHYHIP were higher in African vs. Asian ancestry sPE placentas. Allograft rejection/adaptive immune response genes were upregulated in placentas from African but not in Asian or European ancestry sPE patients; IL3RA was of particular interest because the patient with the highest placental IL3RA expression, a person of African ancestry with sPE, developed postpartum cardiomyopathy, and was the only patient out of 123, that developed this condition. Interestingly, the sPE patients with the highest IL3RA expression among persons of Asian and European ancestries developed unexplained tachycardia peripartum, necessitating echocardiography in the European ancestry patient. The association between elevated placental IL3RA levels and unexplained tachycardia or peripartum cardiomyopathy was found to be significant in the 50 sPE patients (p = .0005).
High placental upregulation of both canonical preeclampsia and allograft rejection/adaptive immune response genes may contribute to worse PE outcomes in African ancestry sPE patients.
与亚洲和欧洲血统的人相比，非洲血统的人患子痫前期（PE）和与 PE 相关的疾病的死亡率要高出 3 到 5 倍。
为了阐明非洲血统妊娠中胎盘对更严重的 PE 结局的贡献，我们对 50 例严重 PE（sPE）的胎盘进行了 bulk RNA 测序，这些胎盘来自非洲（n=9）、亚洲（n=18）和欧洲（n=23）血统的人，以及 73 例非洲（n=10）、亚洲（n=15）和欧洲（n=48）血统的正常血压对照者。
先前描述的经典子痫前期基因，包括参与代谢和缺氧/血管生成的基因：LEP、HK2、FSTL3、FLT1、ENG、TMEM45A、ARHGEF4 和 HTRA1，在所有血统的 sPE 与正常血压胎盘相比均上调。LTF、NPR3 和 PHYHIP 在非洲与亚洲 sPE 胎盘相比更高。非洲 sPE 胎盘的同种异体排斥/适应性免疫反应基因上调，但亚洲或欧洲 sPE 患者的胎盘没有上调；IL3RA 特别引人注目，因为胎盘 IL3RA 表达最高的患者是一位非洲裔 sPE 患者，她产后发生了心肌病，是 123 名患者中唯一发生这种情况的患者。有趣的是，在亚洲和欧洲血统的 sPE 患者中，IL3RA 表达最高的患者在围产期出现了不明原因的心动过速，需要对欧洲血统的患者进行超声心动图检查。在 50 例 sPE 患者中，发现升高的胎盘 IL3RA 水平与不明原因的心动过速或围产期心肌病之间存在显著关联（p=0.0005）。
非洲血统 sPE 患者中胎盘对经典子痫前期和同种异体排斥/适应性免疫反应基因的高上调可能导致更严重的 PE 结局。
