A New Cytokine-Based Immunoassay for the Diagnosis of Lyme Disease

用于诊断莱姆病的新的基于细胞因子的免疫测定法

• 批准号: 8466282
• 负责人: Linda K. Bockenstedt
• 金额: $ 20.32万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-01 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8466282
• 关键词: Affect; Aftercare; Antibiotic Therapy; Antibiotics; Antibodies; Antigens; Autoimmune Diseases; B-Lymphocytes; Biological Assay; Bite; Blood specimen; Borrelia burgdorferi; Cell Communication; Clinical; Communicable Diseases; Complement; Detection; Diagnosis; Diagnostic; Disease; Enzyme-Linked Immunosorbent Assay; Epitopes; Exposure to; Geographic Distribution; Gold; Health Expenditures; Heart; Immunoassay; Immunoblotting; Immunoglobulin G; In Vitro; Incidence; Infection; Infectious Skin Diseases; Inflammatory; Ixodes; Joints; Laboratories; Lead; Lyme Disease; Maps; Measures; Monitor; Morbidity - disease rate; Mus; Nervous system structure; Newly Diagnosed; Order Spirochaetales; Organism; Patients; Peptides; Phase; Physicians; Preventive; Production; Prospective Studies; Proteins; Proteomics; Public Health; Recombinants; Resolution; Rheumatism; Sensitivity and Specificity; Serologic tests; Site; Skin; Specificity; Staging; Subgroup; Symptoms; Syndrome; T cell response; T-Lymphocyte; Techniques; Testing; Ticks; Tissues; Treatment Efficacy; United States; Vector-transmitted infectious disease; Whole Blood; base; cytokine; improved; novel; novel diagnostics; prevent; response; synthetic peptide; tick borne spirochete

DESCRIPTION (provided by applicant): Lyme disease (LD), caused by the Ixodes tick-borne spirochete Borrelia burgdorferi (Bb), is the most common vector-borne disease in the United States. Despite public health preventive measures, the annual confirmed case incidence has risen to nearly 30,000, the vast majority of which occur in the Northeast. Disseminated infection causes disease in the skin, heart, joints and nervous system and can be more difficult to treat. Although antibiotics achieve clinical cure when administered in early stages of infection, delay in diagnosis and treatment can lead to substantial morbidity and health care expenditures for unexplained symptoms that may persist. Timely and accurate diagnosis of LD, therefore, is essential for optimizing treatment and preventing long-term sequelae of the disease. Currently, serologic tests that detect Bb-reactive antibodies are the mainstay of LD diagnostics, but have low sensitivity early in infection, do not distinguish previous exposure to Bb from active infectio, and cannot be used to assess response to therapy. This proposal seeks to improve upon current serologic tests by developing a new diagnostic cytokine assay for LD based on a novel panel of Bb antigens expressed in the skin and/ or required for Bb infection and persistence in the mammalian host. The R21 phase of the proposal will first use a multiplex cytokine assay to determine whether recombinant Bb proteins/synthetic peptides elicit cytokine production from whole blood obtained from patients with newly diagnosed, active LD. We will then optimize the assay conditions, including cytokine selection and Bb protein combination, to produce a refined whole blood cytokine assay that will be further validated in the R33 phase. In a prospective study of a large number of LD subjects and controls conducted during the R33 phase, we will define the sensitivity and specificity of the whole blood cytokine assay and determine whether positive responses in the assay are associated with persistent symptoms after antibiotic treatment. As a strategy that complements current serologic tests, the whole blood cytokine assay will improve the combined sensitivity and specificity of LD diagnostics, especially in situations in which the serologic tests alone under-perform.

描述(申请人提供)：莱姆病(LD)，由硬蜱传播的伯氏疏螺旋体(BB)引起，是美国最常见的媒介传播疾病。尽管采取了公共卫生预防措施，但每年确诊病例已上升至近3万例，其中绝大多数发生在东北地区。播散性感染会导致皮肤、心脏、关节和神经系统疾病，而且可能更难治疗。虽然抗生素在感染的早期阶段就能达到临床治愈的效果，但延迟 对于可能持续存在的不明原因症状，诊断和治疗可能会导致相当大的发病率和医疗费用。因此，及时、准确地诊断LD对于优化治疗和预防该病的长期后遗症至关重要。目前，检测BB反应性抗体的血清学试验是LD诊断的主要方法，但在感染早期敏感性较低，不能区分既往暴露于BB和活动性感染，也不能用于评估治疗的反应。这一建议旨在通过开发一种新的诊断细胞因子试验来改进现有的血清学试验，该试验基于一组在皮肤中表达的和/或哺乳动物宿主中BB感染和持久性所需的BB抗原。该提案的R21阶段将首先使用多重细胞因子试验来确定重组BB蛋白/合成肽是否能从新诊断的活动期LD患者的全血中诱导细胞因子的产生。然后，我们将优化检测条件，包括细胞因子选择和BB蛋白组合，以产生精炼的全血细胞因子检测，并将在R33阶段进一步验证。在R33阶段对大量LD受试者和对照组进行的前瞻性研究中，我们将确定全血细胞因子检测的敏感性和特异性，并确定检测中的阳性反应是否与抗生素治疗后的持续性症状有关。作为对现有血清学检测的补充，全血细胞因子检测将提高LD诊断的敏感性和特异性，特别是在仅用血清学检测效果不佳的情况下。

项目成果

A taxonomic study of Gardnerella vaginalis (Haemophilus vaginalis) Gardner and Dukes 1955.

阴道加德纳菌（阴道嗜血杆菌）Gardner 和 Dukes 的分类学研究，1955 年。

• DOI: 10.1099/00221287-119-2-373
• 发表时间: 1980
• 期刊: Journal of general microbiology
• 作者: Piot,P;vanDyck,E;Goodfellow,M;Falkow,S
• 通讯作者: Falkow,S