■炎症诱导的妊娠组织重塑是自发性早产的基础(sPTB,分娩<37周妊娠)可能因种族和背景而异。为了探索这些病理过程的标志物之间的关系,我们(a)表征了有PTB风险的南非孕妇的宫颈阴道液(CVF)细胞因子谱;(b)测定了CVF基质金属蛋白酶-9(MMP-9)及其金属蛋白酶-1调节组织抑制剂(TIMP-1);(c)探讨了这些标志物对sPTB的预测潜力.
■通过ELISA测定了来自47名PTB高风险的非劳动妇女的CVF样品中10种炎性细胞因子以及MMP-9和TIMP-1的浓度。我们研究了在三个妊娠时间点(GTP)采样的CVF:GTP1(20-22周,n=37),GTP2(26-28周,n=40),和GTP3(34-36周,n=29),并分析了sPTB的蛋白质浓度和预测能力(ROC曲线下面积(AUC)和95%置信区间(CI))的变化。
■有11个(GTP1),13(GTP2),和6名(GTP3)在评估后85.3±25.9、51.3±15.3和11.8±7.5(平均±SD)天内早产的妇女,分别。在GTP1,IL-8更高(4倍,p=0.02),而GM-CSF较低(~1.4倍,p=0.03)在早产与足月女性相比,平均AUC=0.73。在GTP2,IL-1β(18倍,p<0.0001),IL-8(4倍,p=0.03),MMP-9(17倍,p=0.0007),MMP-9/TIMP-1比值(9倍,p=0.004),和MMP-9/GM-CSF比率(87倍,与平均AUC=0.80的足月女性相比,早产的p=0.005)更高。相比之下,IL-10与足月分娩相关,AUC(95%CI)=0.75(0.55-0.90)。在GTP3,IL-1β(58倍,p=0.0003),IL-8(12倍,p=0.002),MMP-9(296倍,p=0.03),和TIMP-1(35倍,与平均AUC=0.85的足月女性相比,早产的p=0.01)更高。IL-1β升高与评估后14天内的分娩相关,AUC=0.85(0.67-0.96)。总的来说,GTP3时MMP-9升高对区分有sPTB风险的女性的阳性似然比最高(13.3).最后,在足月分娩的女性中,MMP-9和TIMP-1在所有GTP(ρ≥0.61,p<0.01)之间呈正相关,仅在早产的女性中在GTP1时观察到(ρ=0.70,p<0.03).
■在此队列中,sPTB与妊娠依赖性促炎细胞因子的增加有关,降低IL-10和GM-CSF,和失调的MMP-9-TIMP-1相互作用。当sPTB即将到来时,在分娩开始前的最后2周内,细胞因子(尤其是IL-1β)和ECM重塑蛋白的水平显着升高。这些ECM重塑观察的信号机制仍有待阐明。
UNASSIGNED: Inflammation-induced remodelling of gestational tissues that underpins spontaneous preterm birth (sPTB, delivery < 37 weeks\' gestation) may vary by race and context. To explore relationships between markers of these pathological processes, we (a) characterised the cervicovaginal fluid (CVF) cytokine profiles of pregnant South African women at risk of PTB; (b) determined CVF matrix-metalloproteinase-9 (MMP-9) and its regulator tissue inhibitor of metalloproteinase-1 (TIMP-1); and (c) explored the predictive potential of these markers for sPTB.
UNASSIGNED: The concentrations of 10 inflammatory cytokines and MMP-9 and TIMP-1 were determined by ELISA in CVF samples from 47 non-labouring women at high risk of PTB. We studied CVF sampled at three gestational time points (GTPs): GTP1 (20-22 weeks, n = 37), GTP2 (26-28 weeks, n = 40), and GTP3 (34-36 weeks, n = 29) and analysed for changes in protein concentrations and predictive capacities (area under the ROC curve (AUC) and 95% confidence interval (CI)) for sPTB.
UNASSIGNED: There were 11 (GTP1), 13 (GTP2), and 6 (GTP3) women who delivered preterm within 85.3 ± 25.9, 51.3 ± 15.3, and 11.8 ± 7.5 (mean ± SD) days after assessment, respectively. At GTP1, IL-8 was higher (4-fold, p = 0.02), whereas GM-CSF was lower (~1.4-fold, p = 0.03) in the preterm compared with term women with an average AUC = 0.73. At GTP2, IL-1β (18-fold, p < 0.0001), IL-8 (4-fold, p = 0.03), MMP-9 (17-fold, p = 0.0007), MMP-9/TIMP-1 ratio (9-fold, p = 0.004), and MMP-9/GM-CSF ratio (87-fold, p = 0.005) were higher in preterm compared with term women with an average AUC = 0.80. By contrast, IL-10 was associated with term delivery with an AUC (95% CI) = 0.75 (0.55-0.90). At GTP3, IL-1β (58-fold, p = 0.0003), IL-8 (12-fold, p = 0.002), MMP-9 (296-fold, p = 0.03), and TIMP-1 (35-fold, p = 0.01) were higher in preterm compared with term women with an average AUC = 0.85. Elevated IL-1β was associated with delivery within 14 days of assessment with AUC = 0.85 (0.67-0.96). Overall, elevated MMP-9 at GTP3 had the highest (13.3) positive likelihood ratio for distinguishing women at risk of sPTB. Lastly, a positive correlation between MMP-9 and TIMP-1 at all GTPs (ρ ≥ 0.61, p < 0.01) for women delivering at term was only observed at GTP1 for those who delivered preterm (ρ = 0.70, p < 0.03).
UNASSIGNED: In this cohort, sPTB is associated with gestation-dependent increase in pro-inflammatory cytokines, decreased IL-10 and GM-CSF, and dysregulated MMP-9-TIMP-1 interaction. Levels of cytokine (especially IL-1β) and ECM remodelling proteins rise significantly in the final 2 weeks before the onset of labour when sPTB is imminent. The signalling mechanisms for these ECM remodelling observations remain to be elucidated.