Departments of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.
Department of Obstetrics and Gynecology, Chungnam National University Hospital, Daejeon, South Korea.
Am J Reprod Immunol. 2024 Aug;92(2):e13913. doi: 10.1111/aji.13913.
To determine whether altered concentrations of various inflammation/immune-, acute phase-, extracellular matrix-, adhesion-, and serine protease-related proteins in the amniotic fluid (AF) are independently associated with microbial invasion of the amniotic cavity and/or intra-amniotic inflammation (MIAC/IAI), imminent spontaneous preterm delivery (SPTD; ≤7 days), and major neonatal morbidity/mortality (NMM) in women with early preterm prelabor rupture of membranes (PPROM).
This was a retrospective cohort study involving 111 singleton pregnant women with PPROM (24-31 weeks) undergoing amniocentesis to diagnose MIAC/IAI. The following proteins were measured in stored AF samples by enzyme-linked immunosorbent assay (ELISA): APRIL, DKK-3, Gal-3BP, IGFBP-2, IL-8, VDBP, lumican, MMP-2, MMP-8, SPARC, TGFBI, TGF-β1, E-selectin, ICAM-5, P-selectin, haptoglobin, hepcidin, SAA1, kallistatin, and uPA.
Multivariate logistic regression analyses revealed that (i) elevated APRIL, IL-8, MMP-8, and TGFBI levels in the AF, reduced lumican and SPARC levels in the AF, and high percentages of samples above the lower limit of quantification for AF TGF-β1 and uPA were significantly associated with MIAC/IAI; (ii) elevated AF levels of IL-8 and MMP-8 were significantly associated with SPTD within 7 days; and (iii) elevated AF IL-6 levels were significantly associated with increased risk for major NMM, when adjusted for baseline covariates.
ECM (lumican, SPRAC, TGFBI, and TGF-β1)- and serine protease (uPA)-associated proteins in the AF are involved in the regulation of the host response to infection/inflammation in the amniotic cavity, whereas AF inflammation (IL-8, MMP-8, and IL-6)-associated mediators are implicated in the development of preterm parturition and major NMM in early PPROM.
确定羊水（AF）中各种炎症/免疫、急性期、细胞外基质、黏附、丝氨酸蛋白酶相关蛋白的浓度变化是否与羊膜腔微生物入侵和/或羊膜内炎症（MIAC/IAI）、即将发生的自发性早产（SPTD；≤7 天）以及患有早发性早产胎膜早破（PPROM）的女性的主要新生儿发病率/死亡率（NMM）独立相关。
这是一项回顾性队列研究，涉及 111 名患有 PPROM（24-31 周）的单胎孕妇，她们接受了羊膜穿刺术以诊断 MIAC/IAI。通过酶联免疫吸附试验（ELISA）在储存的 AF 样本中测量以下蛋白质：APRIL、DKK-3、Gal-3BP、IGFBP-2、IL-8、VDBP、lumican、MMP-2、MMP-8、SPARC、TGFBI、TGF-β1、E-选择素、ICAM-5、P-选择素、触珠蛋白、hepcidin、SAA1、kallistatin 和 uPA。
多变量逻辑回归分析显示，（i）AF 中 APRIL、IL-8、MMP-8 和 TGFBI 水平升高、AF 中 lumican 和 SPARC 水平降低以及 AF TGF-β1 和 uPA 的定量下限以上的样本百分比高与 MIAC/IAI 显著相关；（ii）AF 中 IL-8 和 MMP-8 水平升高与 7 天内 SPTD 显著相关；（iii）调整基线协变量后，AF 中 IL-6 水平升高与主要 NMM 的风险增加显著相关。
AF 中的细胞外基质（lumican、SPARC、TGFBI 和 TGF-β1）和丝氨酸蛋白酶（uPA）相关蛋白参与调节宿主对羊膜腔感染/炎症的反应，而 AF 炎症（IL-8、MMP-8 和 IL-6）相关介质与早产分娩和早期 PPROM 中的主要 NMM 有关。
