Development of a Cytokine Release Assay as a Diagnostic Test for Lyme Disease

开发细胞因子释放测定作为莱姆病的诊断测试

基本信息

  • 批准号:
    8393091
  • 负责人:
  • 金额:
    $ 30万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2012
  • 资助国家:
    美国
  • 起止时间:
    2012-06-15 至 2014-05-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Lyme disease is the most common vector borne infectious disease in North America and Europe. It is a progressive disease with a wide array of clinical manifestations. Treatment of early infection is highly effective, and early diagnosis and treatment are critical to prevent disease progression. By contrast, disseminated late- phase infection is associated with debilitating, sometimes, permanent damage to the nervous and musculoskeletal systems and can be refractory to antibiotics. Currently the laboratory diagnosis of Lyme disease is based on the detection of antibodies against Borrelia burgdorferi in a two-tier serological assay. However, serological assays using native or recombinant proteins from B. burgdorferi as antigens are often insensitive for the detection of antibody present at the time many patients with early Lyme disease usually seek initial medical care and/or lack sufficient specificity as both native and recombinant B. burgdorferi protein antigens contain B cell epitopes that cross react with antibodies against other bacterial species. As a result, it has been estimated that current IgM or IgG Lyme disease assays fail to diagnose early disease in patients ~50% of the time. The failure of serological assays to consistently identify B. burgdorferi infection in patients with suspected Lyme disease necessitates the development of a new class of diagnostic tests. The QuantiFERON(R) assay is a cellular-based IFNg release assay for the detection of antigen-specific T cells in the blood of patients infected with Mycobacterium tuberculosis. This assay, which detects the production of the proinflammatory cytokine IFN? in response to stimulation with peptide antigens derived from M. tuberculosis, has proven to be highly sensitive and highly specific in the diagnosis of tuberculosis, supplanting ineffective serological assays and improving upon diagnosis using the tuberculin skin test. A cellular based assay would represent a new direction in the development of diagnostic assays for Lyme disease, with the potential for being significantly more specific and sensitive than current serological assays. However, the development of such an assay requires the identification of highly-specific peptide epitopes unique to B. burgdorferi. The goal of the current study is to identify unique T cell-epitopes derived from B. burgdorferi proteins for use in a QuantiFERON(R)-based cellular assay for the diagnosis of Lyme disease. PUBLIC HEALTH RELEVANCE: Lyme disease is a clinically progressive disease that can result in permanent debilitating neurological and musculoskeletal damage if the infection is allowed to persist and become disseminated. Early treatment is effective and is critical for the prevention of disseminated disease; however, the currently available diagnostic serologic tests lack sufficient specificity and sensitivity during early disease, and fail to correctly diagnose Lye disease in patients as often as 50% of the time. This application takes an entirely new approach to the design of Lyme disease diagnostics, by focusing on the detection of disease specific T cells in infected individuals using unique peptide antigens to overcome the problems of sensitivity and specificity that plague protein-based serological assays. The result will be the development of an effective diagnostic assay for Lyme disease that will improve disease outcomes in patients through early detection, allowing treatment prior to dissemination.
描述(由申请人提供):莱姆病是北美和欧洲最常见的媒介传播传染病。它是一种进行性疾病,具有多种临床表现。早期感染的治疗非常有效,早期诊断和治疗对于预防疾病进展至关重要。相比之下,播散性晚期感染与神经和肌肉骨骼系统的衰弱性、有时甚至是永久性损伤有关,并且可能对抗生素耐药。目前,莱姆病的实验室诊断基于两级血清学检测中针对伯氏疏螺旋体的抗体检测。然而,使用来自伯氏疏螺旋体的天然或重组蛋白作为抗原的血清学测定通常对于检测许多早期莱姆病患者通常寻求初步医疗护理时存在的抗体不敏感和/或缺乏足够的特异性,因为天然和重组伯氏疏螺旋体蛋白抗原都含有与针对其他细菌物种的抗体交叉反应的B细胞表位。结果,已经 据估计,目前的 IgM 或 IgG 莱姆病检测在大约 50% 的情况下无法诊断患者的早期疾病。 血清学检测未能一致地识别疑似莱姆病患者的伯氏疏螺旋体感染,因此需要开发一类新的诊断测试。 QuantiFERON(R) 测定是一种基于细胞的 IFNg 释放测定,用于检测结核分枝杆菌感染患者血液中的抗原特异性 T 细胞。该检测可检测促炎细胞因子 IFN?已证明,对来自结核分枝杆菌的肽抗原的刺激作出反应,在结核病的诊断中具有高度敏感性和高度特异性,取代了无效的血清学测定,并改进了使用结核菌素皮试的诊断。基于细胞的检测将代表莱姆病诊断检测开发的新方向,有可能比目前的血清学检测更具特异性和敏感性。然而,开发这种检测方法需要鉴定伯氏疏螺旋体特有的高度特异性肽表位。当前研究的目标是鉴定源自伯氏疏螺旋体蛋白的独特 T 细胞表位,用于基于 QuantiFERON(R) 的细胞检测来诊断莱姆病。 公共卫生相关性:莱姆病是一种临床进展性疾病,如果感染持续存在并传播,可能会导致永久性神经衰弱和肌肉骨骼损伤。早期治疗是有效的,对于预防播散性疾病至关重要;然而,目前可用的诊断血清学检测在疾病早期缺乏足够的特异性和敏感性,并且在患者中无法正确诊断碱液病的概率高达 50%。该应用采用了一种全新的莱姆病诊断设计方法,重点是使用独特的肽抗原检测感染个体中的疾病特异性 T 细胞,以克服困扰基于蛋白质的血清学检测的灵敏度和特异性问题。其结果将是开发出一种有效的莱姆病诊断方法,通过早期检测改善患者的疾病结果,从而在传播之前进行治疗。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(1)

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Paul Michael Arnaboldi其他文献

Paul Michael Arnaboldi的其他文献

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{{ truncateString('Paul Michael Arnaboldi', 18)}}的其他基金

A Novel Mucosal Vaccine for Pseudomonas aeruginosa Infection
一种针对铜绿假单胞菌感染的新型粘膜疫苗
  • 批准号:
    10446501
  • 财政年份:
    2022
  • 资助金额:
    $ 30万
  • 项目类别:
A Novel Mucosal Vaccine for Pseudomonas aeruginosa Infection
一种针对铜绿假单胞菌感染的新型粘膜疫苗
  • 批准号:
    10550157
  • 财政年份:
    2022
  • 资助金额:
    $ 30万
  • 项目类别:
A peptide-based point-of-care vertical flow assay for the rapid diagnosis of Lyme disease
基于肽的即时垂直流检测用于快速诊断莱姆病
  • 批准号:
    10404209
  • 财政年份:
    2020
  • 资助金额:
    $ 30万
  • 项目类别:
A peptide-based point-of-care vertical flow assay for the rapid diagnosis of Lyme disease
基于肽的即时垂直流检测用于快速诊断莱姆病
  • 批准号:
    10452660
  • 财政年份:
    2020
  • 资助金额:
    $ 30万
  • 项目类别:
A peptide-based point-of-care vertical flow assay for the rapid diagnosis of Lyme disease
基于肽的即时垂直流检测用于快速诊断莱姆病
  • 批准号:
    10080510
  • 财政年份:
    2020
  • 资助金额:
    $ 30万
  • 项目类别:
A peptide-based point-of-care vertical flow assay for the rapid diagnosis of Lyme disease
基于肽的即时垂直流检测用于快速诊断莱姆病
  • 批准号:
    10653862
  • 财政年份:
    2020
  • 资助金额:
    $ 30万
  • 项目类别:
A peptide-based point-of-care vertical flow assay for the rapid diagnosis of Lyme disease
基于肽的即时垂直流检测用于快速诊断莱姆病
  • 批准号:
    10668819
  • 财政年份:
    2020
  • 资助金额:
    $ 30万
  • 项目类别:
An antigen-capture assay to screen donated blood for Babesia microti
用于筛查捐献血液中是否含有田鼠巴贝虫的抗原捕获测定
  • 批准号:
    9893818
  • 财政年份:
    2019
  • 资助金额:
    $ 30万
  • 项目类别:
A Rapid Point-of-Care Assay for the Diagnosis of Lyme Disease
诊断莱姆病的快速护理点检测
  • 批准号:
    9135755
  • 财政年份:
    2016
  • 资助金额:
    $ 30万
  • 项目类别:
Peptide-based Multiplex Assay for Lyme disease Serodiagnosis
基于肽的莱姆病血清学诊断多重检测
  • 批准号:
    9045060
  • 财政年份:
    2016
  • 资助金额:
    $ 30万
  • 项目类别:

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