Antibody isotyping for discrimination of disease stage and diagnosis of early Lyme disease.

用于区分疾病阶段和诊断早期莱姆病的抗体同种型。

• 批准号: 10080461
• 负责人: Maria Gomes-Solecki
• 金额: $ 29.81万
• 依托单位: IMMUNO TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10080461
• 关键词: Acute; Acute Disease; Affinity; Antibodies; Antibody Response; Antigens; Arthritis; Benchmarking; Biological Assay; Biological Markers; Borrelia burgdorferi; Centers for Disease Control and Prevention (U.S.); Clinic; Clinical; Collaborations; Data; Development; Diagnosis; Diagnostic; Diagnostic Specificity; Discrimination; Disease; Early Diagnosis; Enzyme Immunoassay; Evaluation; GTP-Binding Protein alpha Subunits, Gs; Genetic Recombination; Goals; Grant; High Prevalence; Human; IgA1; IgA2; IgE; IgG1; IgG2; IgG3; IgG4; Immune response; Immunodominant Antigens; Immunoglobulin A; Immunoglobulin D; Immunoglobulin G; Immunoglobulin Isotypes; Immunoglobulin M; Immunoglobulins; Infection; Iowa; Laboratories; Laboratory Diagnosis; Lateral; Lesion; Letters; Licensing; Lyme Arthritis; Lyme Disease; Machine Learning; OspC protein; Patients; Peptidoglycan; Performance; Phase; Proteins; ROC Curve; Recommendation; Reproducibility; Research; Serum; Small Business Innovation Research Grant; Specificity; Techniques; Technology; Testing; Time; Training; Universities; Update; V(D)J Recombination; Visual; Work; antigen binding; base; commercialization; disease diagnosis; erythema migrans; follow-up; improved; novel diagnostics; pathogen; tool

ABSTRACT More than 3 million tests are performed each year to support the laboratory diagnosis of human Lyme disease (LD). While the CDC conventional standard two-tier (CSTT) approach for serodiagnosis of LD has worked relatively well when used as recommended, there is plenty of room for improvement. Of a number of weaknesses associated with the supplemental immunoblot of the CSTT the most significant is low reproducibility due to the subjective visual interpretation of results. To overcome these weaknesses the CDC recently updated its recommendations based on a modified STT (MSTT) in that a second EIA can replace the immunoblot. The major goal of this project is to develop an objective, quantitative, multiplex EIA that can detect four antibody isotypes (IgM/D/G/A) and all four IgG subclasses (IgG1/2/3/4) to leverage acquisition of simultaneous antibody profile information on multiple B. burgdorferi antigens to build an assay that can discriminate Lyme disease stage with increased overall sensitivity without incurring in loss of specificity. The novelty of this study relies on: 1) evaluation of B. burgdorferi antigen-specific antibody isotypes and IgG subclasses that can be correlated with Lyme disease stage; and 2) development of new diagnostic tools using machine learning techniques to train and integrate all data and produce an objective result to discriminate early Lyme from early disseminated/late Lyme disease. We expect this Phase I SBIR to allow us to develop a new EIA for serodiagnosis of Lyme disease (isoEIAplex-Ld) and to further an ongoing collaboration with DCN diagnostics for the adaptation of our biomarkers to a new rapid Lateral Flow Assay (see Letter of Support) for a follow up Phase II SBIR .

抽象的 每年进行超过 300 万次测试以支持人类莱姆病的实验室诊断 疾病（LD）。虽然 CDC 传统的标准两层 (CSTT) 方法用于血清学诊断 当按照建议使用时，LD 的效果相对较好，还有很大的改进空间。 在与 CSTT 补充免疫印迹相关的众多弱点中，最重要的是 显着的是由于结果的主观视觉解释导致再现性低。克服 针对这些弱点，CDC 最近根据修改后的 STT (MSTT) 更新了其建议 因为第二次 EIA 可以取代免疫印迹。该项目的主要目标是开发一个 客观、定量、多重 EIA，可检测四种抗体同种型 (IgM/D/G/A) 以及所有四种 IgG 子类 (IgG1/2/3/4)，以利用同时获取的抗体谱信息 多种伯氏疏螺旋体抗原构建了一种可以区分莱姆病阶段的检测方法 提高总体敏感性而不损失特异性。本研究的新颖性在于： 1) 评估伯氏疏螺旋体抗原特异性抗体同种型和 IgG 亚类 与莱姆病阶段相关； 2）使用机器开发新的诊断工具 学习技术来训练和整合所有数据并产生客观结果以进行早期区分 来自早期播散性/晚期莱姆病的莱姆病。我们预计第一阶段 SBIR 将使我们能够开发 用于莱姆病血清诊断的新 EIA​​ (isoEIAplex-Ld) 并进一步推进正在进行的合作 与 DCN 诊断一起使我们的生物标志物适应新的快速侧向层析检测（参见 支持信）用于后续第二阶段 SBIR 。