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
- 来源:
- 关键词:AntibioticsAntibodiesAntigensAreaB-Lymphocyte EpitopesBacteriaBiological AssayBloodBlood specimenBorrelia burgdorferiCaringCellsCellular AssayClinicalDetectionDevelopmentDiagnosisDiagnosticDiagnostic testsDiseaseDisease OutcomeDisease ProgressionEarly DiagnosisEarly treatmentEnzyme-Linked Immunosorbent AssayEpitopesEquilibriumEuropeFDA approvedFailureGoalsImmunoglobulin GImmunoglobulin MIndividualInfectionInflammatoryInterferonsInterleukin-17Interleukin-2Laboratory DiagnosisLeadLyeLyme DiseaseManufacturer NameMeasurableMeasuresMedicalMonitorMusculoskeletalMusculoskeletal SystemMycobacterium tuberculosisNervous system structureNeurologicNorth AmericaOutcomePatientsPeptide LibraryPeptidesPhasePlaguePreventionProcessProductionProgressive DiseaseProteinsRecombinant ProteinsRecombinantsRefractoryResearchSamplingSensitivity and SpecificitySerologic testsSerologicalSpecificityStagingT-LymphocyteT-Lymphocyte EpitopesTestingTimeTreatment EfficacyTuberculin TestTuberculosisUnited StatesVector-transmitted infectious diseaseWestern BlottingWhole BloodWorkbasecell typecross reactivitycytokinedesignexpectationimprovednovel strategiespreventprotein Bresponsesuccess
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的传染病。它是一种进行性疾病,具有广泛的临床表现。早期感染的治疗非常有效,早期诊断和治疗对于防止疾病进展至关重要。相比之下,播散性晚期感染与神经和肌肉骨骼系统的衰弱有关,有时是永久性损伤,并且抗生素可能难以治疗。目前,莱姆病的实验室诊断是基于在两级血清学测定中检测针对伯氏疏螺旋体的抗体。然而,使用来自B的天然或重组蛋白质的血清学测定。作为抗原的伯氏疏螺旋体通常对检测早期莱姆病患者通常寻求初始医疗护理时存在的抗体不敏感和/或缺乏作为天然和重组B的足够特异性。伯氏菌蛋白抗原含有与抗其它细菌物种的抗体交叉反应的B细胞表位。因此,
据估计,目前的IgM或IgG莱姆病检测无法诊断早期疾病的患者约50%的时间。 血清学检测无法一致地识别B。疑似莱姆病患者中的伯氏菌感染需要开发一类新的诊断测试。QuantiFERON(R)检测试剂盒是一种基于细胞的IFNg释放检测试剂盒,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。该试验,检测促炎细胞因子IFN?对来自M.结核菌素皮肤试验已被证明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善了使用结核菌素皮肤试验的诊断。基于细胞的测定将代表莱姆病诊断测定发展的新方向,具有比当前血清学测定显著更特异和更灵敏的潜力。然而,这种测定法的开发需要鉴定B特有的高度特异性肽表位。burgdorferi。本研究的目的是鉴定源自B的独特T细胞表位。用于诊断莱姆病的基于QuantiFERON(R)的细胞测定的伯氏螺旋体蛋白。
公共卫生关系:莱姆病是一种临床进展性疾病,如果感染持续并扩散,可导致永久性神经和肌肉骨骼损伤。早期治疗是有效的,对于预防传播性疾病至关重要;然而,目前可用的诊断血清学测试在早期疾病中缺乏足够的特异性和敏感性,并且在50%的情况下无法正确诊断患者的莱伊病。该应用采用了一种全新的方法来设计莱姆病诊断,通过专注于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测定的灵敏度和特异性问题。其结果将是开发一种有效的莱姆病诊断检测方法,通过早期检测改善患者的疾病结局,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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