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

摘要 每年进行超过300万次检测，以支持人类莱姆病的实验室诊断 疾病（LD）。虽然CDC用于血清学诊断的常规标准两层（CSTT）方法 LD在按照建议使用时工作得相对较好，有很大的改进空间。 在与CSTT的补充免疫印迹相关的许多弱点中， 重要的是由于结果的主观视觉解释而导致的低再现性。克服 针对这些弱点，疾病预防控制中心最近根据修改后的短期培训计划（MSTT）更新了其建议 因为第二EIA可以代替免疫印迹。该项目的主要目标是开发一个 客观，定量，多重EIA，可以检测四种抗体同种型（IgM/D/G/A）和所有四种 IgG亚类（IgG 1/2/3/4），以利用同时采集的抗体谱信息， 多个B。莱姆病抗原，建立一个检测，可以区分莱姆病阶段与 增加了总体灵敏度，而不会导致特异性损失。本研究的新奇依赖于： 1)评价B。可用于本发明的抗原特异性抗体同种型和IgG亚类 与莱姆病分期相关; 2）使用机器开发新的诊断工具 学习训练和整合所有数据的技术，并产生客观的结果，以早期区分 莱姆病早期播散性/晚期。我们希望第一阶段SBIR能够让我们开发 莱姆病血清学诊断的新EIA（isoEIAplex-Ld），并促进正在进行的合作 与DCN诊断相结合，使我们的生物标志物适应新的快速侧向流测定（参见 支持信），以进行后续第二阶段SBIR。

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 .