Table_1_Influenza-Induced Interferon Lambda Response Is Associated With Longer Time to Delivery Among Pregnant Kenyan Women.docx

Specific causes of preterm birth remain unclear. Several recent studies have suggested that immune changes during pregnancy are associated with the timing of delivery, yet few studies have been performed in low-income country settings where the rates of preterm birth are the highest. We conducted a retrospective nested case-control evaluation within a longitudinal study among HIV-uninfected pregnant Kenyan women. To characterize immune function in these women, we evaluated unstimulated and stimulated peripheral blood mononuclear cells in vitro with the A/California/2009 strain of influenza to understand the influenza-induced immune response. We then evaluated transcript expression profiles using the Affymetrix Human GeneChip Transcriptome Array 2.0. Transcriptional profiles of sufficient quality for analysis were obtained from 54 women; 19 of these women delivered 37 weeks. The median time to birth from sample collection was 13 weeks. No transcripts were significantly associated with preterm birth in a case-control study of matched term and preterm birth (n = 42 women). In the influenza-stimulated samples, expression of IFNL1 was associated with longer time to delivery—the amount of time between sample collection and delivery (n = 54 women). A qPCR analysis confirmed that influenza-induced IFNL expression was associated with longer time to delivery. These data indicate that during pregnancy, ex vivo influenza stimulation results in altered transcriptional response and is associated with time to delivery in cohort of women residing in an area with high preterm birth prevalence.

早产的具体原因尚不明确。近期多项研究指出，孕期免疫系统的变化与分娩时机存在关联，然而，在早产率最高的低收入国家环境中，相关研究却鲜有开展。本研究在一项针对未感染艾滋病的肯尼亚孕妇的纵向研究中，对早产病例进行了回顾性嵌套病例对照评估。为描绘这些女性的免疫功能，我们采用体外实验，以流感A/加州/2009株对未刺激和刺激的周围血单个核细胞进行检测，以探究流感引发的免疫反应。随后，我们利用Affymetrix Human GeneChip Transcriptome Array 2.0对转录表达谱进行评估。从54名女性中获得了足以分析的转录组学质量数据；其中19名女性在37周时分娩。从样本采集到分娩的中位时间为13周。在一项针对足月与早产（共42名女性）的病例对照研究中，未发现任何转录本与早产显著相关。在流感刺激的样本中，IFNL1的表达与分娩时间延长相关——即样本采集与分娩之间的时间（共54名女性）。qPCR分析证实，流感引发的IFNL表达与分娩时间延长有关。这些数据表明，在孕期，体外流感刺激导致转录反应发生改变，并与居住在高早产率地区女性的分娩时间相关。