人类妊娠急性肾盂肾炎的外周全血转录组。
The peripheral whole-blood transcriptome of acute pyelonephritis in human pregnancya.
出版信息
J Perinat Med. 2014 Jan;42(1):31-53. doi: 10.1515/jpm-2013-0085.
OBJECTIVE
Human pregnancy is characterized by activation of the innate immune response and suppression of adaptive immunity. The former is thought to provide protection against infection for the mother, and the latter, tolerance against paternal antigens expressed in fetal cells. Acute pyelonephritis is associated with an increased risk of acute respiratory distress syndrome and sepsis in pregnant (vs. nonpregnant) women. The objective of this study was to describe the gene expression profile (transcriptome) of maternal whole blood in acute pyelonephritis.
METHOD
A case-control study was conducted to include pregnant women with acute pyelonephritis (n=15) and women with a normal pregnancy (n=34). Affymetrix HG-U133 Plus 2.0 arrays (Affymetrix, Santa Clara, CA, USA) were used for gene expression profiling. A linear model was used to test the association between the presence of pyelonephritis and gene expression levels while controlling for white blood cell count and gestational age. A fold change of 1.5 was considered significant at a false discovery rate of 0.1. A subset of differentially expressed genes (n=56) was tested with real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) (cases, n=19; controls, n=59). Gene ontology and pathway analyses were applied.
RESULTS
A total of 983 genes were differentially expressed in acute pyelonephritis: 457 were upregulated and 526 were downregulated. Significant enrichment of 300 biological processes and 63 molecular functions was found in pyelonephritis. Significantly impacted pathways in pyelonephritis included (a) cytokine-cytokine receptor interaction, (b) T-cell receptor signaling, (c) Jak-STAT signaling, and (d) complement and coagulation cascades. Of 56 genes tested by qRT-PCR, 48 (85.7%) had confirmation of differential expression.
CONCLUSION
This is the first study of the transcriptomic signature of whole blood in pregnant women with acute pyelonephritis. Acute infection during pregnancy is associated with the increased expression of genes involved in innate immunity and the decreased expression of genes involved in lymphocyte function.
目的
人类妊娠的特点是先天免疫反应的激活和适应性免疫的抑制。前者被认为可以为母亲提供针对感染的保护，而后者则为胎儿细胞中表达的父系抗原提供耐受性。急性肾盂肾炎与孕妇（与非孕妇相比）急性呼吸窘迫综合征和败血症的风险增加有关。本研究的目的是描述急性肾盂肾炎孕妇全血的基因表达谱（转录组）。
方法
进行了一项病例对照研究，纳入了 15 例急性肾盂肾炎孕妇和 34 例正常妊娠孕妇。使用 Affymetrix HG-U133 Plus 2.0 阵列（Affymetrix，圣克拉拉，加利福尼亚州，美国）进行基因表达谱分析。使用线性模型测试肾盂肾炎的存在与基因表达水平之间的关联，同时控制白细胞计数和孕龄。假发现率为 0.1 时，倍数变化 1.5 被认为具有统计学意义。使用实时定量逆转录聚合酶链反应（qRT-PCR）（病例，n=19；对照，n=59）对一组差异表达基因（n=56）进行了测试。应用了基因本体论和途径分析。
结果
急性肾盂肾炎共表达了 983 个差异表达基因：457 个上调，526 个下调。在肾盂肾炎中发现了 300 个生物过程和 63 个分子功能的显著富集。肾盂肾炎中受显著影响的途径包括（a）细胞因子-细胞因子受体相互作用，（b）T 细胞受体信号，（c）Jak-STAT 信号，和（d）补体和凝血级联。在通过 qRT-PCR 测试的 56 个基因中，有 48 个（85.7%）的差异表达得到了证实。
结论
这是第一项关于孕妇急性肾盂肾炎全血转录组特征的研究。妊娠期间的急性感染与参与先天免疫的基因表达增加和参与淋巴细胞功能的基因表达减少有关。
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