Immunodiagnostic Tests for the Rapid Diagnosis of Tb

描述（由申请人提供）：这是一份修改后的申请，来自Jacqueline Achkar医学博士，她是阿尔伯特爱因斯坦医学院的医学助理教授。她的长期目标是成为一名独立的研究者，从事与结核病（TB）、艾滋病毒及其合并感染相关的临床转化研究。该职业发展计划将为她提供临床研究方法、免疫学、分子技术、流行病学、决策分析和生物统计学等方面的深入培训。结核病是全球主要的公共卫生问题，也是艾滋病患者死亡的主要原因。为了实现美国疾病控制与预防中心消除结核病的目标，改善全球结核病控制，以及在发展为晚期疾病之前识别和治疗活动性结核病，迫切需要早期准确诊断肺结核（PTB）。目前，尚无高灵敏度和高特异性的快速检测方法可用于诊断所有类型的活动性结核病。该候选人建议检验结核分枝杆菌两种免疫优势蛋白抗体检测的准确性和临床价值，以快速诊断肺结核。该建议的中心假设是，对这两种蛋白质的抗体反应包含足够的信息，相对于公认的金标准，可以为PTB提供准确的血清诊断测试。该试验可作为一种有用的辅助手段，以提高常规快速检测PBT的灵敏度。本项目的具体目的是：(1)评估基于蛋白的ELISA的敏感性、特异性及临床应用价值；(2)测定两种蛋白的总免疫球蛋白（Ig）浓度、Ig同型和IgG亚类的滴度，并比较hiv感染和未感染PTB患者的免疫球蛋白浓度和滴度；(3)检验新鉴定的结核分枝杆菌抗原是否能在不影响特异性的前提下提高基于蛋白的ELISA的敏感性。这将是一项前瞻性研究。在两年的时间里，将从纽约市的几家医院招募连续接受肺结核临床评估的成年患者（n=500）；按照金标准，125/500（25%）预计患有结核病，40%的登记患者预计感染艾滋病毒。血清抗体对结核分枝杆菌免疫优势蛋白的反应性结果将与培养、组织学或临床证实的结核分枝杆菌的金标准进行比较。将对200名随机选择的诊断为肺结核以外肺部疾病的培养阴性受试者进行特异性评估。

DESCRIPTION (provided by applicant): This is a revised application from Jacqueline Achkar, M.D., who is an Assistant Professor in Medicine at the Albert Einstein College of Medicine. Her long-term goal is to become an independent investigator in clinical translational research related to tuberculosis (TB), HIV, and their occurrence as co-infections. The proposed career development plan will provide her with in-depth training in clinical research methods, immunology, molecular techniques, epidemiology, decision-making analysis and biostatistics. TB is a global leading public health problem and the leading cause of death in people with AIDS. There is an urgent need for early and accurate diagnosis of pulmonary TB (PTB) to achieve the CDC goal of elimination of TB in the US, improve TB control worldwide, and identify and treat active TB before development of advanced disease. Currently, there are no rapid tests with high sensitivity and specificity available for the diagnosis of all classes of active TB. The candidate proposes to examine the accuracy and clinical value of antibody detection to two immunodominant proteins of M. tb for the rapid diagnosis of PTB. The central hypothesis of this proposal is that antibody responses to these two proteins contain sufficient information to provide an accurate serodiagnostic test for PTB relative to an accepted gold standard. This test can serve as an useful adjunct to enhance the sensitivity of conventional rapid tests for PBT. The specific aims of this project are: (1) To assess the sensitivity, specificity and clinical value of the protein-based ELISA; (2) To determine total immunoglobulin (Ig) concentrations and titers of Ig isotypes and IgG subclasses to the two proteins, and compare them between HIV-infected and HIV-uninfected PTB patients; and (3) To test whether newly identified antigens of M. tb will enhance the sensitivity of the protein-based ELISA without compromising its specificity. This will be a prospective study. Consecutive adult patients (n=500) undergoing clinical evaluation for PTB will be enrolled from several hospital sites in New York City over a period of two years; 125/500 (25%) are expected to have TB by gold standard, and 40% of the enrolled patients are expected to be HIV-infected. The results of serum antibody reactivity to the immunodominant proteins of M. tb will be compared to the gold standard of culture, histological or clinically proven PTB. Specificity will be assessed in 200 randomly selected culture-negative subjects who are diagnosed with a pulmonary disease other than PTB.