Kim Hyeon Ji, Park Kyo Hoon, Joo Eunwook, Lee Jung Yun, Im Eun Mi, Lee Kyong-No, Shin Sue
Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.
Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul National University Boramae Hospital, Seoul, South Korea.
Am J Reprod Immunol. 2023 May;89(5):e13697. doi: 10.1111/aji.13697. Epub 2023 Mar 30.
To investigate whether altered expression of various inflammation-, angiogenesis-, and extracellular matrix-related mediators in cervicovaginal fluid (CVF) could be independently associated with acute histological chorioamnionitis (HCA), microbial-associated HCA, and funisitis in women with preterm premature rupture of membranes (PPROM).
Clinical data of 102 consecutive singleton pregnant women with PPROM at 23+0 to 34+0 weeks were retrospectively analyzed. CVF samples were collected upon admission. Levels of APRIL, DKK-3, IGFBP-1/2, IL-6/8, lipocalin-2, M-CSF, MIP-1α, MMP-8/9, S100A8A9, TGFBI, TIMP-1, TNFR2, uPA, and VDBP were determined by ELISA. Placentas were histologically examined after birth.
Multivariate logistic regression analyses showed that: (1) elevated CVF levels of IL-8 and TNFR2 were independently associated with acute HCA; (2) elevated CVF levels of IL-6, IL-8, M-CSF, MMP-8, and TNFR2 were independently associated with microbial-associated HCA; and (3) elevated CVF IL-8 and MMP-8 levels were independently associated with funisitis when adjusted for gestational age. Areas under the curves of the aforementioned CVF biomarkers ranged within 0.61-0.77, thereby demonstrating poor to fair diagnostic capacity for these clinical endpoints. HCA risk significantly increased as the CVF levels of each inflammatory mediator increased (P for trend < 0.05).
Herein, we identified several inflammatory biomarkers (IL-6/8, M-CSF, MMP-8, and TNFR2) in the CVF that are independently associated with acute HCA, microbial-associated HCA, and funisitis in women with PPROM. Furthermore, the degree of inflammatory response in the CVF, based on the levels of these proteins, demonstrated a direct relationship with HCA risk (especially risk severity).
探讨宫颈阴道液（CVF）中各种炎症、血管生成和细胞外基质相关介质的表达改变是否与胎膜早破（PPROM）孕妇的急性组织学绒毛膜羊膜炎（HCA）、微生物相关的HCA及脐带炎独立相关。
回顾性分析102例孕周在23⁺⁰至34⁺⁰周连续单胎PPROM孕妇的临床资料。入院时采集CVF样本。采用酶联免疫吸附测定法（ELISA）测定增殖诱导配体（APRIL）、Dickkopf相关蛋白3（DKK-3）、胰岛素样生长因子结合蛋白1/2（IGFBP-1/2）、白细胞介素6/8（IL-6/8）、脂质运载蛋白2、巨噬细胞集落刺激因子（M-CSF）、巨噬细胞炎性蛋白-1α（MIP-1α）、基质金属蛋白酶8/9（MMP-8/9）、钙结合蛋白A8/A9（S100A8A9）、转化生长因子β诱导蛋白（TGFBI）、金属蛋白酶组织抑制剂-1（TIMP-1）、肿瘤坏死因子受体2（TNFR2）、尿激酶型纤溶酶原激活剂（uPA）和维生素D结合蛋白（VDBP）的水平。出生后对胎盘进行组织学检查。
多因素logistic回归分析显示：（1）CVF中IL-8和TNFR2水平升高与急性HCA独立相关；（2）CVF中IL-6、IL-8、M-CSF、MMP-8和TNFR2水平升高与微生物相关的HCA独立相关；（3）校正孕周后，CVF中IL-8和MMP-8水平升高与脐带炎独立相关。上述CVF生物标志物的曲线下面积在0.61 - 0.77范围内，表明对这些临床终点的诊断能力较差至中等。随着每种炎症介质的CVF水平升高，HCA风险显著增加（趋势P < 0.05）。
在此，我们在CVF中鉴定出几种炎症生物标志物（IL-6/8、M-CSF、MMP-8和TNFR2），它们与PPROM孕妇的急性HCA、微生物相关的HCA及脐带炎独立相关。此外，基于这些蛋白质水平的CVF炎症反应程度与HCA风险（尤其是风险严重程度）呈直接关系。
