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

描述（由申请方提供）：脑囊虫病（NCC）是一种脑部寄生虫感染，占印度韦洛雷地区活动性癫痫病例的34%。目前急需新的方法来诊断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患者被抗体检测的金标准所遗漏。最近的数据表明，宿主的免疫应答对于确定NCC感染的表现是重要的。因此，使用现有技术的方法分析非抗体宿主应答提供了一种新的和合乎逻辑的方法，用于推进NCC检测的知识。 这项美国-印度提案的长期目标是确定用于诊断NCC相关癫痫的新型循环生物标志物。本提案的目的是在美国俄克拉荷马州健康科学中心（OUHSC）和印度基督教医学院（CMC）的研究者之间建立有效的合作，并测试电喷雾电离质谱（ESI-MS）血清分析和血液单核细胞mRNA表达分析在多大程度上代表了更好地检测NCC及其表现的创新工具。 合作伙伴关系的目标是将流行病学/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起来。在研究目标1中，我们将测试ESI-MS血清分析可以开发一组小分子标志物的程度，以区分CMC鉴定的NCC相关癫痫患者和特征良好的对照组。在研究目的2中，我们将分析血液单核细胞的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与使用目标1和2的结果对患者进行分类的传统方法。 在印度韦洛雷举行的第一次会议上，将评估科学家和研究生交流的机会以及培训需求。将组织一次关于贝叶斯统计的讲习班。研究部分将包括收集血液和血清从病人参加临床服务的部门。神经科学中心将选择四组患者：1）NCC相关活动性癫痫/癫痫发作患者; 2）NCC患者恢复至少2年; 3）无NCC或囊虫病证据的活动性癫痫/癫痫发作患者; 4）无NCC、囊虫病和脑CT扫描正常的患者。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。将结果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的mRNA表达谱和ESI-MS是否可用于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）区分NCC病变类型。

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.