Immunodiagnostic Tests for the Rapid Diagnosis of Tb

描述(由申请人提供)：这是艾伯特·爱因斯坦医学院医学助理教授、医学博士杰奎琳·阿奇卡修改后的申请。她的长期目标是成为与结核病(TB)、艾滋病毒及其合并感染相关的临床转化研究的独立研究员。拟议的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。迫切需要对肺结核(PTB)进行早期和准确的诊断，以实现美国疾控中心消除结核病的目标，改善全球的结核病控制，并在晚期疾病发展之前识别和治疗活动性结核病。目前，还没有高灵敏度和高特异度的快速检测方法可用于诊断所有类型的活动性结核病。候选人建议检查两种结核分枝杆菌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。这一建议的中心假设是，对这两种蛋白的抗体反应包含了足够的信息，可以提供相对于公认的金标准的准确的肺结核血清诊断试验。这项检测可以作为一种有用的辅助手段来提高传统PBT快速检测的敏感性。本项目的具体目的是：(1)评估基于蛋白的ELISA的敏感性、特异性和临床价值；(2)测定总免疫球蛋白(Ig)浓度和针对这两种蛋白的Ig亚型和Ig亚类滴度，并比较HIV感染和未感染HIV的肺结核患者；(3)测试新发现的结核分枝杆菌抗原是否会在不影响其特异性的情况下提高基于蛋白的ELISA法的敏感性。这将是一项前瞻性研究。连续接受肺结核临床评估的成人患者(n=500)将在两年内从纽约市的几家医院登记；根据黄金标准，125/500(25%)预计会患上结核病，登记的患者中预计有40%是艾滋病毒感染的。对结核分枝杆菌免疫优势蛋白的血清抗体反应结果将与培养、组织学或临床证实的肺结核的金标准进行比较。将在200名随机选择的培养阴性受试者中进行特异性评估，这些受试者被诊断为患有肺结核以外的肺部疾病。

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.