Understanding the inflammatory processes of neurocysticercosis: a US-India partne

描述(申请人提供)：神经囊虫病(NCC)是一种脑部寄生虫感染，占印度韦洛尔区活动性癫痫病例的34%。迫切需要新的方法来诊断NCC患者。诊断成像的费用超出了大多数患者的承受能力，34%的NCC患者被抗体检测的黄金标准漏掉了。最近的数据表明，宿主免疫反应对于确定NCC感染的表现很重要。因此，使用最先进的方法分析非抗体宿主反应为提高检测NCC的知识提供了一种新的和合乎逻辑的方法。这项美国-印度提案的长期目标是识别新的循环生物标记物，用于诊断NCC相关性癫痫。这项提议的目的是在大学的调查人员之间建立有效的协作。美国俄克拉何马州健康科学中心(OUHSC)和印度基督教医学院(CMC)的一项研究，并测试电喷雾电离质谱仪(ESI-MS)的血清图谱和分析血单核细胞的mRNA表达在多大程度上是更好地检测NCC及其表现的创新工具。合作伙伴关系目标将流行病学/生物统计学、单核细胞生物学和生物化学方面的专业知识与NCC的临床和免疫学专业知识结合在一起。在研究目标1中，我们将测试ESI-MS的血清图谱可以在多大程度上发展出一组小分子标志物，以区分CMC确诊的NCC相关性癫痫患者和特征良好的对照组。在研究目的2中，我们将分析外周血单核细胞的mRNA表达，以确定癫痫患者中NCC患者的基因表达特征。研究目标3将比较序贯朴素贝叶斯统计分类方法和使用目标1和2的结果对患者进行分类的传统方法。在印度韦洛尔举行的第一次会议期间，将评估科学家和研究生交流的机会以及培训需求。将组织一个关于贝叶斯统计的讲习班。研究部分将包括从前往本部临床服务的患者收集血液和血清。神经科学，CMC。将选择四组患者：1)NCC相关的活动性癫痫/癫痫患者；2)NCC患者康复至少2年；3)无NCC或囊虫病证据的活动性癫痫/癫痫患者；4)无NCC、囊虫病和正常脑部CT扫描的患者。血清分析将在OUHSC进行，而单核细胞分离和mRNA表达分析将在CMC进行。结果将与金标准抗体和抗原检测方法进行比较。这项研究将使我们能够确定单核细胞和ESI-MS的mRNA表达谱是否可以用于1)识别癫痫病例，2)识别NCC相关癫痫病例，3)描述病变消退后炎症过程的演变，以及4)鉴别NCC病变的类型。

DESCRIPTION (provided by applicant): Neurocysticercosis (NCC) is a parasitic infection of the brain that accounts for 34% of active epilepsy cases in Vellore district, India. New methods for diagnosing patients with NCC are badly needed. The cost of diagnostic imaging is beyond the means of most patients, and 34% of NCC patients are missed by the gold standard for antibody detection. Recent data suggest that host immune responses are important for determining manifestations of NCC infection. Thus, analyses of non-antibody host responses using state of the art methods present a novel and logical approach for advancing knowledge in detection of NCC. The long-term objective of this US-India proposal is to identify novel circulating biomarkers for diagnosis for NCC-associated epilepsy. The purposes of this proposal are to establish an effective collaboration among investigators from the Univ. of Oklahoma Health Sciences Center (OUHSC), USA, and the Christian Medical College (CMC), India, and to test the extent to which serum profiling by electrospray ionization mass spectrometry (ESI-MS) and analysis of mRNA expression in blood monocytes represent innovative tools for better detection of NCC and its manifestations. The Collaborative partnership aim brings together expertise in epidemiology/biostatistics, monocyte biology and biochemistry with clinical and immunological expertise in NCC. In Research Aim 1, we will test the extent to which serum profiling by ESI-MS can develop of panel of small molecular markers to distinguish patients with NCC-associated epilepsy identified at CMC from well-characterized controls. In Research Aim 2, we will analyze mRNA expression of blood monocytes to identify gene expression signatures characteristic of NCC patients among people with epilepsy. Research Aim 3 will compare a sequential na¿ve Bayes statistical classification approach to the traditional approach to classify patients using results from Aims 1 and 2. During an initial meeting in Vellore, India, opportunities for exchange of scientists and graduate students as well as needs in training will be assessed. A workshop on Bayesian statistics will be organized. The research component will include collection of blood and sera from patients attending the clinical services of Dept. of Neurological Sciences, CMC. Four groups of patients will be selected: 1) patients with NCC-associated active epilepsy/seizures; 2) NCC patients recovered for at least 2 years; 3) patients with active epilepsy/seizures without evidence of NCC or cysticercosis; 4) patients without NCC, cysticercosis, and a normal brain CT scan. Serum profiling will be conducted at OUHSC, whereas monocyte isolation and analysis of mRNA expression will be conducted at CMC. Results will be compared with gold-standard antibody and antigen detection methods. This research will allow us to determine if mRNA expression profiling of monocytes and ESI-MS can be used to 1) identify cases of epilepsy, 2) identify cases of NCC-associated epilepsy, 3) describe the evolution of the inflammatory process post resolution of the lesions and 4) differentiate between types of NCC lesions.