Defining Campylobacter and immune response related determinants in the pathogenesis of Guillain-Barré syndrome patients in low-income countries

定义低收入国家格林-巴利综合征患者发病机制中弯曲杆菌和免疫反应相关的决定因素

• 批准号: 10612447
• 负责人: Zhahirul Islam
• 金额: $ 10.43万
• 依托单位: INTERNATIONAL CTR/DIARRHOEAL DIS RES
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-08 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10612447
• 关键词: Academic Medical Centers; Address; Affect; All-Trans-Retinol; Bangladesh; Belief; Biological Markers; Blood; Body mass index; C-reactive protein; Campylobacter; Campylobacter jejuni; Caring; Clinical; Clinical Course of Disease; Data; Development; Disease; Disease Outcome; Epidemiology; Genetic Determinism; Genomics; Goals; Guillain Barré Syndrome; Health; High-Throughput Nucleotide Sequencing; Hospitals; IL17 gene; Immune response; Immunoglobulin G; Immunoglobulin Therapy; Immunologic Markers; Incidence; Infection; Infrastructure; Interferon Type II; Interleukin-1 beta; Interleukin-10; Interleukin-4; Interleukin-6; Intravenous Immunoglobulins; Knowledge; Liver Function Tests; Maps; Measures; Mentors; Monitor; Netherlands; Neurosciences; Nutritional; Nutritional status; Outcome; Pathogenesis; Patient Care; Patient-Focused Outcomes; Patients; Phenotype; Poliomyelitis; Prediction of Response to Therapy; Predictive Factor; Prognosis; Program Development; Recommendation; Recovery; Research; Research Personnel; Research Project Grants; Residual state; Role; Serum; Serum Albumin; Severity of illness; Socioeconomic Status; Supportive care; TNF gene; Testing; Texas; Training; Training Activity; Treatment outcome; Universities; Washington; Zinc; career development; clinical outcome measures; clinical predictors; cohort; cost; design; disability; effective therapy; genetic variant; genome sequencing; genome wide association study; improved; individual patient; insight; low income country; microbial; mortality; outcome prediction; pathogen; personalized medicine; potential biomarker; prospective; research and development; response; skills; standard care; treatment response; whole genome

Project Summary Since the eradication of poliomyelitis, Guillain-Barré syndrome (GBS) has become a major health burden in low-income countries. The prognosis of GBS has not improved over the last two decades. Our group previously showed that the incidence, disease severity and mortality of GBS are higher in Bangladesh compared to the developed world. The preferred and most effective treatment for severe GBS is intravenous immunoglobulin (IVIg), yet some patients respond poorly to this recommended therapy. Little is known about the factors that influence disease pathogenesis and recovery in patients receiving IVIg therapy in low-income countries. Our long-term goal is to identify key determinants that predict IVIg treatment response in patients with GBS from low-income countries. The main hypothesis of the proposed project is that biological markers, nutritional factors or microbial strain differences may potentially influence the response of IVIg or clinical course and outcome of patients with GBS in low-income countries. Our objective is to identify key determinants to measure IVIg treatment responsiveness in patients with GBS in Bangladesh. Our specific aims will test the following hypotheses: Specific aim #1: We will identify whether biological markers serve as predictive factors to determine IVIg treatment response or whether nutritional status affects IVIg treatment response, the clinical course and GBS disease outcome in a low-income country. Specific aim #2: We will use high- throughput sequencing to generate and compare the whole genome sequences of Campylobacter jejuni strains isolated from IVIg-treated and non-treated patients with GBS, in order to identify the key genetic determinants responsible for disease pathogenesis and outcomes of IVIg treatment in low-income countries. The research proposed in this career development application is built upon ongoing, long-standing collaborative efforts between the icddr,b (Bangladesh), Erasmus University Medical Centre (the Netherlands), the University of Texas (USA), Washington State University (USA) and the National Institute of Neurosciences & Hospital (Bangladesh). The goal of this Career Development Program is to strengthen the skills necessary to become an independent researcher/investigator in host-pathogen interaction and advanced genomics research.

项目摘要 自消灭脊髓灰质炎以来，格林-巴利综合征（GBS）已成为一种主要的健康 低收入国家的负担。GBS的预后在过去两年中没有改善 几十年我们的研究小组先前表明，GBS的发病率、疾病严重程度和死亡率 与发达国家相比，孟加拉国的死亡率更高。首选和最有效的 严重GBS的治疗是静脉注射免疫球蛋白（IVIg），但有些患者对 这种推荐的疗法效果不佳。人们对影响疾病的因素知之甚少 在低收入国家接受IVIg治疗的患者中，我们 长期目标是确定预测患者IVIg治疗反应的关键决定因素 来自低收入国家的GBS。拟议项目的主要假设是， 生物标志物、营养因素或微生物菌株差异可能潜在地影响 IVIg的反应或低收入国家GBS患者的临床病程和结局。 我们的目标是确定关键的决定因素，以衡量静脉注射免疫球蛋白治疗的反应， 孟加拉国的GBS患者。我们的具体目标将测试以下假设： 目的#1：我们将确定生物标志物是否可作为预测因子来确定IVIg 治疗反应或营养状况是否影响IVIg治疗反应， 低收入国家的病程和GBS疾病结局。具体目标#2：我们将使用高- 通量测序，以生成并比较 从IVIg治疗和未治疗的GBS患者中分离的空肠弯曲杆菌菌株， 为了确定负责疾病发病机制的关键遗传决定因素， 低收入国家的IVIg治疗结果。在这个职业生涯中提出的研究 开发应用程序是建立在持续的，长期的合作努力之间的 icddr，B（孟加拉国）、伊拉斯谟大学医学中心（荷兰）、伊拉斯谟大学 德克萨斯大学（美国）、华盛顿州立大学（美国）和国家神经科学研究所 和医院（孟加拉国）。该职业发展计划的目标是加强 必要的技能，成为一个独立的研究员/调查员在宿主病原体 互动和先进的基因组学研究。