Yonekura Collier Ai-Ris, Zsengeller Zsuzsanna, Pernicone Elizabeth, Salahuddin Saira, Khankin Eliyahu V, Karumanchi S Ananth
a Department of Obstetrics and Gynecology , Beth Israel Deaconess Medical Center , Boston , MA , USA.
b Department of Obstetrics and Gynecology and Reproductive Biology , Harvard Medical School , Boston , MA , USA.
Hypertens Pregnancy. 2019 Aug;38(3):193-199. doi: 10.1080/10641955.2019.1640725. Epub 2019 Jul 10.
The immune complement system protects against pathogens; however, excess activation results in disease like hemolytic uremic syndrome, a clinical imitator of preeclampsia. Vascular endothelial factor (VEGF) protects against aberrant complement activation and is inhibited by soluble fms-like tyrosine kinase-1 (sFLT1) in other organs. We hypothesize that sFLT1 promotes complement-mediated placental damage through VEGF inhibition in preeclampsia. Quantify placental complement activity and sFLT1 expression in preeclampsia, and the subgroup of preeclampsia with hemolysis elevated liver enzymes low platelets (HELLP) syndrome. Placental complement activation marker C4d, membrane attack complex (MAC), and sFLT1 expression was quantified using immunofluores cence microscopy. Placentas from 18 controls, 25 preeclampsia, including 6 cases of HELLP syndrome were identified. Placental C4d expression was greater in PE (median 6.4 [IQR: 5.1, 8.3]) compared to controls (4.4 [3.6, 5.5]; p = 0.003). MAC expression was also increased in preeclampsia compared to controls (6.5 [5.8, 8.7]; 5.4 [2.9, 5.9], p = 0.001). Placental sFLT1 expression was also higher in preeclampsia (p <0.0001). C4d and MAC were strongly correlated with sFLT1 levels in the placenta (R = 0.72; p < 0.0001 and R = 0.59; p = 0.01, respectively). Complement and sFLT1 expression was elevated in HELLP compared to preeclampsia without laboratory abnormalities, but this difference did not reach statistical significance. Increased placental complement activation and damage was seen in preeclampsia and correlates with sFLT1 expression. Our findings support the importance of the complement pathway in preeclampsia.
免疫补体系统可抵御病原体；然而，过度激活会导致诸如溶血尿毒综合征等疾病，后者是子痫前期的临床模仿者。血管内皮因子（VEGF）可防止补体异常激活，在其他器官中它受可溶性fms样酪氨酸激酶-1（sFLT1）抑制。我们假设在子痫前期，sFLT1通过抑制VEGF促进补体介导的胎盘损伤。量化子痫前期以及伴有溶血、肝酶升高和血小板减少（HELLP）综合征的子痫前期亚组中的胎盘补体活性和sFLT1表达。使用免疫荧光显微镜定量胎盘补体激活标志物C4d、膜攻击复合物（MAC）和sFLT1表达。鉴定了来自18例对照、25例子痫前期（包括6例HELLP综合征病例）的胎盘。与对照组（4.4 [3.6, 5.5]；p = 0.003）相比，子痫前期胎盘C4d表达更高（中位数6.4 [四分位间距：5.1, 8.3]）。与对照组相比，子痫前期MAC表达也增加（6.5 [5.8, 8.7]；5.4 [2.9, 5.9]，p = 0.001）。子痫前期胎盘sFLT1表达也更高（p <0.0001）。C4d和MAC与胎盘中sFLT1水平密切相关（分别为R = 0.72；p <0.0001和R = 0.59；p = 0.01）。与无实验室异常的子痫前期相比，HELLP中补体和sFLT1表达升高，但这种差异未达到统计学意义。子痫前期可见胎盘补体激活和损伤增加，且与sFLT1表达相关。我们的研究结果支持补体途径在子痫前期中的重要性。
