Department of Statistics, Stanford University, Stanford, CA, United States.
Department of Data Science and Knowledge Engineering, Maastricht University, Maastricht, Netherlands.
Front Immunol. 2020 Mar 17;11:452. doi: 10.3389/fimmu.2020.00452. eCollection 2020.
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 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 <34 weeks and were defined as preterm cases and 35 controls 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, 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.
早产的确切原因仍不清楚。最近的几项研究表明，怀孕期间的免疫变化与分娩时间有关，但在早产率最高的低收入国家进行的此类研究较少。我们在肯尼亚未感染艾滋病毒的孕妇中进行了一项纵向研究的回顾性巢式病例对照评估。为了描述这些女性的免疫功能，我们用 A/California/2009 流感株评估了未刺激和刺激的外周血单核细胞，以了解流感引起的免疫反应。然后，我们使用 Affymetrix Human GeneChip Transcriptome Array 2.0 评估了转录表达谱。从 54 名女性中获得了足够质量进行分析的转录谱；其中 19 名女性在 <34 周时分娩，被定义为早产病例，35 名女性在 >37 周时分娩，作为对照。从样本采集到分娩的中位时间为 13 周。在一项匹配足月和早产的病例对照研究（n = 42 名女性）中，没有转录物与早产显著相关。在流感刺激样本中，IFNL1 的表达与分娩时间（n = 54 名女性）之间的时间有关。qPCR 分析证实，流感诱导的 IFNL 表达与分娩时间有关。这些数据表明，在怀孕期间，流感刺激会导致转录反应改变，并与高早产率地区女性队列的分娩时间有关。
