Endotoxin Neutralization as a Biomonitor for HIV Disease Progression

内毒素中和作为 HIV 疾病进展的生物监测器

• 批准号: 8790322
• 负责人: Keith Champion
• 金额: $ 15万
• 依托单位: BIODTECH, INC.
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8790322
• 关键词: Acquired Immunodeficiency Syndrome; Address; Affect; Age; Bacterial Translocation; Biological Assay; Biological Markers; Biological Monitoring; Blood Circulation; CD14 gene; CD4 Positive T Lymphocytes; Cell Count; Chronic; Clinic; Clinical; Collection; Control Groups; Detection; Disease; Disease Progression; Elements; Endotoxins; Evaluation; Funding; Gastrointestinal tract structure; HIV; HIV Infections; HIV Seropositivity; Health; Human; Immune system; Immunoglobulins; Inflammatory; Inflammatory Bowel Diseases; Inflammatory Response; Interleukin-1; Intestines; Measures; Medical; Methods; Monitor; Mortality Determinants; Pathology; Patient Monitoring; Patients; Permeability; Phase; Plasma; Preparation; Publishing; Recording of previous events; Research Personnel; Sampling; Severities; Severity of illness; Small Business Innovation Research Grant; Source; Specimen; Students; System; Technology; Testing; Tumor Necrosis Factor-alpha; United States; Viral; Viral Load result; base; cost; cytokine; demographics; immune activation; lipopolysaccharide-binding protein; male; meetings; mortality; novel; patient population; public health relevance; response; tool; user-friendly

DESCRIPTION (provided by applicant): Endotoxin neutralization in human plasma is an excellent indicator of chronic immune activation, which is the most accurate predictor of mortality in HIV. Recently we developed an assay using endotoxin neutralization as an indicator of bacterial translocation. This assay is accurate in discriminating control patients from those with inflammatory bowel disease in addition to indicating disease severity. We propose to adapt our endotoxin neutralization assay for the evaluation of HIV disease severity and progression. In the 6 month Phase I part of the SBIR project, we will (1) collect plasma from 20 19-50 year old HIV-positive males and an equivalent number of demographically similar HIV-negative male subjects and test for viral load and CD4+ T cell count, (2) measure the levels of specific plasma markers indicative of bacterial translocation, immune system activation and/or inflammatory response, and (3) measure immune activation using our endotoxin neutralization biomarker monitor system. Once a neutralization profile of each sample is established, Pearson correlation will be used to determine the relationship between endotoxin neutralization and all factors established in the first two aims. Student's T-test will be used to determine statistical significance between HIV- positive and control groups. The results from Phase I will show whether our endotoxin neutralization system is a convenient, reproducible and inexpensive method to assess the severity of HIV disease. In Phase II of the project, we will use our system to monitor patients over a 1-2 year period to correlate endotoxin neutralization with treatment.

描述(由申请人提供)：人体血浆中的内毒素中和是慢性免疫激活的一个很好的指标，这是最准确的艾滋病毒死亡率预测指标。最近，我们开发了一种使用内毒素中和作为细菌易位指标的检测方法。除了提示疾病的严重程度外，这项检测还能准确地区分炎症性肠病患者和对照组患者。我们建议采用我们的内毒素中和试验来评估HIV疾病的严重程度和进展。在SBIR项目为期6个月的第一阶段中，我们将(1)收集20名19-50岁HIV阳性男性和同等数量人口统计学上相似的HIV阴性男性受试者的血浆，并测试病毒载量和CD4+T细胞计数，(2)测量指示细菌易位、免疫系统激活和/或炎症反应的特定血浆标志物的水平，以及(3)使用我们的内毒素中和生物标志物监测系统测量免疫激活。一旦建立了每个样本的中和曲线，将使用皮尔逊相关性来确定内毒素中和与前两个目标中建立的所有因素之间的关系。学生的T检验将被用来确定HIV阳性组和对照组之间的统计学意义。第一阶段的结果将表明，我们的内毒素中和系统是否是评估艾滋病毒疾病严重程度的方便、可重复和廉价的方法。在该项目的第二阶段，我们将使用我们的系统在1-2年的时间内监测患者，以将内毒素中和与治疗联系起来。