Proteomic biomarker analysis of amniotic fluid for identification of intra-amniotic inflammation
Proteomic biomarker analysis of amniotic fluid for identification of intra-amniotic inflammation
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DOI：
10.1111/j.1471-0528.2004.00340.x
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发表时间：
2005-02-01
影响因子：
5.8
通讯作者：
Buhimschi, CS
中科院分区：
文献类型：
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作者：
Buhimschi, IA;Christner, R;Buhimschi, CS
背景：羊膜腔内炎症与新生儿预后不良相关，与早产无关。我们应用蛋白质组学技术（SELDI：表面增强激光解吸电离），以确定羊膜内inflammation.Design的蛋白质组学概况一百零四个样本的羊水进行了分析。在第1阶段，对来自具有早产症状和已知结果的患者的样本进行测试，以确定炎症的特征性特征。我们提取的配置文件使用一种新的，逐步的逻辑方法比较SELDI跟踪从早产和羊膜内炎症反应感染的患者的跟踪谁有早产的症状，但在足月分娩的患者。在第二阶段，我们将算法应用于研究者未知结果的妊娠样本。设置北美大学与Ciphergen现场示范实验室合作。从经腹子宫穿刺术中采集104份人类羊水样本。（表面增强激光解吸电离）和质量限制分析，一种从蛋白质组学SELDI示踪中提取临床和生物学相关生物标志物的新算法。主要结果测量导致早产的羊膜内炎症和/或感染的存在。导致早产的羊水炎症具有以下三种或四种蛋白质的独特羊水蛋白质组谱：中性粒细胞防御素-1和-2，以及钙颗粒蛋白A和C。基于这些生物标志物的存在或不存在，我们设计了范围从0（所有生物标志物峰不存在）到4（所有生物标志物峰存在）的质量限制（MR）评分。在第1阶段，MR评分> 2对于检测羊膜内炎症具有92.9%的敏感性（95%CI 76.5-98.9）和91.8%的特异性（95%CI 80.4-97.7）。在盲法测试（第2阶段）中，MR评分> 2提供了100%的特异性和灵敏度（95% CI 100-100）。结论羊水蛋白质组学分析揭示了子宫内炎症特征性生物标志物的存在。这种方法可以确定可能从预防宫内胎儿损伤的干预措施中获益最多的患者亚组。
Background Intra-amniotic inflammation is associated with poor neonatal outcome independent of prematurity. We applied proteomic technology (SELDI: surface-enhanced laser desorption ionisation) to identify the proteomic profile of intra-amniotic inflammation.Design One hundred and four samples of amniotic fluid were analysed. In stage 1, samples from patients with symptoms of preterm labour and known outcomes were tested to identify the characteristic profile for inflammation. We extracted the profile using a novel, stepwise logical approach comparing SELDI tracings from patients who delivered preterm and had intra-amniotic inflammation in response to infection to the tracings of patients who had symptoms of preterm labour but delivered at term. In stage 2, we applied the algorithm to samples from pregnancies whose outcomes were unknown to the investigators.Setting North-American university in collaboration with Ciphergen field demonstration laboratory.Sample One hundred and four samples of human amniotic fluid from transabdominal amniocentesis.Methods SELDI (surface-enhanced laser desorption ionisation) and Mass Restricted analysis, a novel algorithm for extraction of clinical and biological relevant biomarkers from proteomic SELDI tracings.Main outcome measure Presence of intra-amniotic inflammation and/or infection leading to preterm birth.Results Patients with intra-amniotic inflammation that deliver preterm have a distinctive amniotic fluid proteomic profile of three or four of the following proteins: neutrophil defensins-1 and -2, and calgranulins A and C. Based on the presence or absence of these biomarkers, we devised the mass restricted (MR) score ranging from 0 (all biomarker peaks absent) to 4 (all biomarker peaks present). In stage 1, MR score > 2 had 92.9% sensitivity (95% CI 76.5-98.9) and 91.8% specificity (95% CI 80.4-97.7) for detection of intra-amniotic inflammation. In blind testing (stage 2), MR score > 2 provided 100% specificity and sensitivity (95% CI 100-100). A MR score > 2 was associated with imminent preterm delivery.Conclusion Proteomic analysis of amniotic fluid reveals the presence of biomarkers characteristic of intrauterine inflammation. This methodology may identify the subgroup of patients that might benefit most from interventions to prevent fetal damage in utero.