Using Host Responses to Neurocysticercosis to Develop Novel, Brain-imaging Free Diagnostics: a US-India Partnership

利用宿主对神经囊尾蚴病的反应来开发新颖的脑成像免费诊断方法:美印合作

基本信息

项目摘要

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 NCC are badly needed because 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. Our National Institute of Neurological Disease and Stroke (R21NS077466) and Indian Ministry of Science and Technology (BT/MB/BRCP/06/2011)-funded pilot study used mRNA arrays of blood monocytes followed by qPCR confirmation to identify differentially expressed genes in patients with NCC- associated seizures / epilepsy (referred to as epilepsy) compared to controls with and without epilepsy. This approach identified 15 genes of interest showing highest expression levels in patients with NCC-associated epilepsy, followed by patients with resolved NCC and finally by those with idiopathic epilepsy. Expression levels of some genes differed among NCC patients with different types of brain lesions with expression decreasing as lesions resolved. In addition, sera from the same patients were analyzed by electrospray ionization mass spectrometry (ESI-MS) to identify mass/charge peaks that could discriminate between NCC patients and controls. Notably, ESI-MS also distinguished NCC from idiopathic seizures / epilepsy, and both ESI-MS and gene expression studies identified overexpression of RAP1A at the protein levels and mRNA levels, respectively, in NCC patients. These results are extremely promising for developing novel diagnostic tools. Our central hypothesis is that NCC-associated epilepsy can be diagnosed by peripheral biomarkers and will be tested with two research specific aims. Specific Aim 1 will establish the relevance of preliminarily identified candidate genes to NCC. In a first sub-aim, we will assess in-vitro relationships between exposure to T. solium metacestodes' antigens and expression of candidate genes in patient monocytes and in monocyte- like cell lines. The second sub-aim will measure candidate gene expression in monocytes prospectively in NCC patients during therapy and as their lesions change, and will be compared with expression levels of the same genes in whole blood. Specific Aim 2 will identify the proteins/peptides causing differentially expressed mass peaks in serum of patients with NCC-associated seizures and confirm their specificity to NCC. Tandem MS/MS will be used to identify proteins linked to ESI-MS mass peaks that discriminate between NCC-associated seizures and other group of patients. Capacity Building Aim 1 will train one junior faculty member and one research fellow in the use of mass spectrometry as a diagnostic tool. Capacity Building Aim 2 will train laboratory personnel at all levels in cellular and molecular techniques used to study host responses to infection. Successful completion of these aims will identify candidate biomarkers of NCC-associated seizures for field testing and determine their ability to predict different types of NCC-related lesions. Local expertise will be developed in India to conduct these studies and pursue novel insights into the biology of NCC.
脑囊虫病(NCC)是一种脑寄生虫感染,占活动性癫痫病例的34 在印度的韦洛雷区。诊断NCC的新方法是迫切需要的,因为诊断的成本 影像学检查超出了大多数患者的能力,34%的NCC患者被金标准遗漏, 抗体检测我们的国家神经疾病和中风研究所(R21 NS 077466)和印度 科学技术部(BT/MB/BRCP/06/2011)资助的使用血液mRNA阵列的试点研究 单核细胞,然后进行qPCR确认,以鉴定NCC患者中差异表达的基因。 相关的癫痫发作/癫痫(称为癫痫)与有和无癫痫的对照相比。这 一种方法确定了15个感兴趣的基因,这些基因在NCC相关的患者中表达水平最高。 癫痫,其次是NCC消退的患者,最后是特发性癫痫患者。表达 不同类型脑损伤的NCC患者中某些基因的表达水平不同, 随着病变消退而降低。此外,通过电喷雾分析来自相同患者的血清, 离子化质谱(ESI-MS),以识别可区分NCC 患者和对照组。值得注意的是,ESI-MS还区分了NCC与特发性癫痫发作/癫痫,并且两者都是 ESI-MS和基因表达研究鉴定了RAP 1A在蛋白水平和mRNA水平的过表达。 分别在NCC患者中的水平。这些结果对于开发新的诊断方法非常有希望。 工具.我们的中心假设是,NCC相关癫痫可以通过外周生物标志物进行诊断, 将以两个特定的研究目标进行测试。具体目标1将初步确定 确定NCC的候选基因。在第一个子目标中,我们将评估体外暴露于 T.后绦虫抗原和候选基因在患者单核细胞和单核细胞中的表达, 比如细胞系第二个子目标将在NCC中前瞻性地测量单核细胞中的候选基因表达。 患者在治疗过程中和他们的病变变化,并将与相同的表达水平进行比较, 全血中的基因特定目标2将识别引起差异表达质量的蛋白质/肽 NCC相关癫痫发作患者血清中的峰,并证实其对NCC的特异性。串联MS/MS 将用于鉴定与ESI-MS质量峰相关的蛋白质, 癫痫和其他组患者。能力建设目标1将培训一名初级教员和一名 研究人员在使用质谱作为诊断工具。能力建设目标2将培训 在细胞和分子技术方面的各级实验室人员,用于研究宿主对 感染成功完成这些目标将确定NCC相关癫痫发作的候选生物标志物 进行现场测试,并确定其预测不同类型的NCC相关病变的能力。当地专家将 在印度开发,进行这些研究,并寻求新的见解NCC的生物学。

项目成果

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Helene Carabin其他文献

Helene Carabin的其他文献

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{{ truncateString('Helene Carabin', 18)}}的其他基金

Understanding the inflammatory processes of neurocysticercosis: a US-India partne
了解神经囊尾蚴病的炎症过程:美印合作伙伴
  • 批准号:
    8337851
  • 财政年份:
    2011
  • 资助金额:
    $ 51.68万
  • 项目类别:
Understanding the inflammatory processes of neurocysticercosis: a US-India partne
了解神经囊尾蚴病的炎症过程:美印合作伙伴
  • 批准号:
    8246179
  • 财政年份:
    2011
  • 资助金额:
    $ 51.68万
  • 项目类别:
EFECAB: Improving pig management to prevent epilepsy in Burkina Faso
EFECAB:改善布基纳法索的生猪管理以预防癫痫
  • 批准号:
    8133621
  • 财政年份:
    2010
  • 资助金额:
    $ 51.68万
  • 项目类别:
EFECAB: Improving pig management to prevent epilepsy in Burkina Faso
EFECAB:改善布基纳法索的生猪管理以预防癫痫
  • 批准号:
    8259694
  • 财政年份:
    2010
  • 资助金额:
    $ 51.68万
  • 项目类别:
EFECAB: Improving pig management to prevent epilepsy in Burkina Faso
EFECAB:改善布基纳法索的生猪管理以预防癫痫
  • 批准号:
    8459530
  • 财政年份:
    2010
  • 资助金额:
    $ 51.68万
  • 项目类别:
EFECAB: Improving pig management to prevent epilepsy in Burkina Faso
EFECAB:改善布基纳法索的生猪管理以预防癫痫
  • 批准号:
    7846576
  • 财政年份:
    2010
  • 资助金额:
    $ 51.68万
  • 项目类别:
EFECAB: Improving pig management to prevent epilepsy in Burkina Faso
EFECAB:改善布基纳法索的生猪管理以预防癫痫
  • 批准号:
    8644952
  • 财政年份:
    2010
  • 资助金额:
    $ 51.68万
  • 项目类别:
EFECAB: Improving pig management to prevent epilepsy in Burkina Faso
EFECAB:改善布基纳法索的生猪管理以预防癫痫
  • 批准号:
    8077436
  • 财政年份:
    2010
  • 资助金额:
    $ 51.68万
  • 项目类别:
HIV-CNS Diseases and Parasitic Zoonoses in the Eastern Cape, South Africa
南非东开普省的 HIV-CNS 疾病和人畜共患寄生虫病
  • 批准号:
    7849589
  • 财政年份:
    2009
  • 资助金额:
    $ 51.68万
  • 项目类别:
Epidemiology and Burden of Neurocysticercosis in Bukina Faso
布基纳法索神经囊尾蚴病的流行病学和负担
  • 批准号:
    7244100
  • 财政年份:
    2006
  • 资助金额:
    $ 51.68万
  • 项目类别:

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