Using proteomics in perinatal and neonatal sepsis: hopes and challenges for the future.
Using proteomics in perinatal and neonatal sepsis: hopes and challenges for the future.
复制标题
DOI：
10.1097/qco.0b013e32832a5963
复制
发表时间：
2009-06
影响因子：
3.9
通讯作者：
Buhimschi IA
中科院分区：
文献类型：
--
作者：
Buhimschi CS;Bhandari V;Han YW;Dulay AT;Baumbusch MA;Madri JA;Buhimschi IA
胎儿对感染的免疫反应的特殊性导致炎症状态升高，与微生物侮辱协同作用，诱导损伤。蛋白质组学为检测有败血症和神经损伤风险的胎儿提供了机会。分子工具（16S-rRNA）表明羊膜内感染的微生物因子的多样性超过了临床怀疑或培养记录。由此产生的炎症过程有可能损害子宫内的胎儿。逐步算法[质量限制（MR）评分]已被开发用于提取羊水（AF）炎症特征的蛋白质组学谱。MR评分包括4个蛋白质组学生物标志物：防御素-2、防御素-1、S100A12和S100A8蛋白。其他与早产相关的房颤生物标志物有S100A9和胰岛素样生长因子结合蛋白1 （IGFBP-1）。S100A12是晚期糖基化终末产物受体（RAGE）的配体，与组织学绒毛膜羊膜炎和尿道炎的相关性最强。在房颤中存在S100A12和S100A8可预测早发性新生儿脓毒症和不良的神经发育结局。房颤蛋白组学炎症生物标志物的存在与出生时胎儿炎症状态的增加有关。未来的挑战是寻找生物标志物，以深入了解慢性胎儿和新生儿细胞损伤的分子机制，并确定早期神经保护策略的候选物。
Particularities of the fetal immune response to infection cause a heightened inflammatory state that acts synergistically with microbial insult to induce damage. Proteomics offers the opportunity for detecting fetuses at risk of sepsis and neurological injury. Molecular tools (16S-rRNA) demonstrate the diversity of microbial agents of intra-amniotic infection exceeds what is suspected clinically or is documented by cultures. The resulting inflammatory process has the potential to damage the fetus in utero. Stepwise algorithms [mass restricted (MR) score] have been developed to extract proteomic profiles characteristic of amniotic fluid (AF) inflammation. The MR score includes 4 proteomic biomarkers: defensin-2, defensin-1, S100A12 and S100A8 proteins. Other AF biomarkers relevant for preterm birth are S100A9 and insulin-like-growth-factor-binding protein 1 (IGFBP-1). S100A12, ligand for the receptor of advanced glycation end-products (RAGE), has the strongest association with histological chorioamnionitis and funisitis. Presence of S100A12 and S100A8 in AF is predictive of early-onset neonatal sepsis and poor neuro-developmental outcome. Presence of AF proteomic biomarkers of inflammation is associated with increased inflammatory status of the fetus at birth. Future challenges are finding biomarkers that provide insight into molecular mechanisms of chronic fetal and neonatal cellular damage and identify candidates for early neuro-protection strategies.