Comparative proteomics of cerebrospinal fluid reveals a predictive model for differential diagnosis of pneumococcal, meningococcal, and enteroviral meningitis, and novel putative therapeutic targets.
Comparative proteomics of cerebrospinal fluid reveals a predictive model for differential diagnosis of pneumococcal, meningococcal, and enteroviral meningitis, and novel putative therapeutic targets.
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DOI：
10.1186/1471-2164-16-s5-s11
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发表时间：
2015
期刊：
影响因子：
4.4
通讯作者：
Coimbra RS
中科院分区：
文献类型：
--
作者：
Cordeiro AP;Silva Pereira RA;Chapeaurouge A;Coimbra CS;Perales J;Oliveira G;Sanchez Candiani TM;Coimbra RS
脑膜炎是脑膜对感染或化学试剂的反应的炎症。虽然无菌性脑膜炎，最常见的是由肠道病毒引起的，通常是良性的，具有自限性过程，但细菌性脑膜炎仍然与高发病率和死亡率相关，尽管抗菌治疗和重症监护取得了进展。快速和准确的鉴别诊断是至关重要的自信选择适当的治疗方法，为每一种形式的脑膜炎。我们使用2D-PAGE和质谱鉴定与宿主对肺炎球菌、脑膜炎球菌和肠道病毒性脑膜炎的反应特异相关的脑脊液蛋白质组。通过途径分析检查疾病特异性蛋白质组特征。独特的脑脊液蛋白质组签名被发现的三种病因学形式的脑膜炎的调查，和一个定性预测模型与四个蛋白质标记物的这些疾病的鉴别诊断。然而，疾病特异性蛋白质组的通路分析揭示，激肽释放酶-激肽系统可能在导致细菌性脑膜炎脑损伤的病理生理机制中起着至关重要的作用。参与这一细胞过程的蛋白质被认为是新的抗肿瘤治疗的假定靶点。脑脊液的比较蛋白质组学揭示了候选的生物标志物，这些生物标志物结合在定性和序贯预测模型中，有可能提高肺炎球菌、脑膜炎球菌和肠道病毒性脑膜炎的鉴别诊断。此外，我们提出了第一个证据的可能含义的激肽释放酶-激肽系统在细菌性脑膜炎的病理生理。
Meningitis is the inflammation of the meninges in response to infection or chemical agents. While aseptic meningitis, most frequently caused by enteroviruses, is usually benign with a self-limiting course, bacterial meningitis remains associated with high morbidity and mortality rates, despite advances in antimicrobial therapy and intensive care. Fast and accurate differential diagnosis is crucial for assertive choice of the appropriate therapeutic approach for each form of meningitis. We used 2D-PAGE and mass spectrometry to identify the cerebrospinal fluid proteome specifically related to the host response to pneumococcal, meningococcal, and enteroviral meningitis. The disease-specific proteome signatures were inspected by pathway analysis. Unique cerebrospinal fluid proteome signatures were found to the three aetiological forms of meningitis investigated, and a qualitative predictive model with four protein markers was developed for the differential diagnosis of these diseases. Nevertheless, pathway analysis of the disease-specific proteomes unveiled that Kallikrein-kinin system may play a crucial role in the pathophysiological mechanisms leading to brain damage in bacterial meningitis. Proteins taking part in this cellular process are proposed as putative targets to novel adjunctive therapies. Comparative proteomics of cerebrospinal fluid disclosed candidate biomarkers, which were combined in a qualitative and sequential predictive model with potential to improve the differential diagnosis of pneumococcal, meningococcal and enteroviral meningitis. Moreover, we present the first evidence of the possible implication of Kallikrein-kinin system in the pathophysiology of bacterial meningitis.