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

项目摘要 自消灭脊髓灰质炎以来，格林-巴利综合征(GBS)已成为一种主要卫生疾病 低收入国家的负担。在过去的两年中，GBS的预后并没有改善。 几十年。我们小组先前的研究表明，GBS的发病率、疾病严重程度和死亡率 与发达国家相比，孟加拉国的这一比例更高。首选和最有效的 重症GBS的治疗是静脉注射免疫球蛋白(IVIg)，但一些患者有反应 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。 低收入国家接受IVIg治疗的患者的发病机制和康复。我们的 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。提议的项目的主要假设是 生物标志物、营养因素或微生物菌株的差异可能会潜在地影响 低收入国家GBS患者静脉注射免疫球蛋白的反应或临床病程和结果。 我们的目标是确定衡量IVIg治疗反应性的关键决定因素 孟加拉国的GBS患者。我们的具体目标将检验以下假设：具体 目标1：我们将确定生物标志物是否可以作为预测因素来确定IVIg 治疗反应或营养状况是否影响IVIg治疗反应，临床 低收入国家的病程和GBS疾病结局。具体目标2：我们将使用HIGH 进行吞吐量测序，以生成和比较该病毒的全基因组序列 从静脉注射免疫球蛋白治疗和未治疗的GBS患者中分离到空肠弯曲杆菌 为了找出导致疾病发生和发展的关键基因决定因素 低收入国家静脉注射免疫球蛋白治疗的结果。在这一职业生涯中提出的研究 开发应用程序建立在持续的、长期的合作努力之上 ICDDR，b(孟加拉国)，伊拉斯谟大学医学中心(荷兰)，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 &医院(孟加拉国)。这项职业发展计划的目标是加强 成为寄主病原体的独立研究员/调查者所需的技能 相互作用和先进的基因组研究。

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.