Diagnosis and Pathogenesis of Early Lyme Disease

描述(由申请人提供)：这项赠款提案的目标是改进莱姆病的诊断测试，并确定导致更严重疾病的螺旋体和宿主因素。这一目标将通过对莱姆病患者的大规模、回顾性和前瞻性系列患者的样本分析来实现。对于该项目，将前瞻性地评估领先的候选第二代血清学检测，即IgM OspC(C10)多肽ELISA和Ig G vise(IR6)多肽ELISA，并将其与早期或晚期莱姆病患者和对照组的全细胞超声ELIoA和Western印迹结果进行比较。我们将探索伯氏杆菌新糖脂抗原的抗体反应，以了解抗生素治疗后对这些反应的连续测定是否可以作为螺旋体杀灭的潜在替代标记。定量聚合酶链式反应作为莱姆病患者的诊断试验的价值将与标准的聚合酶链式反应和培养相比较。移行性红斑(EM)皮肤病变的皮肤活检样本中的螺旋体负荷以及这些皮损分离株中的螺旋体毒力因子将被描绘出来，结果将与螺旋体扩散的临床标志和感染的严重程度相关联。最后，将测定这些患者EM皮损中的细胞因子和趋化因子谱，并将其与螺旋体扩散和感染严重程度的临床标志物以及细胞和体液免疫功能的血液测试结果相关联。这些研究可能为莱姆病的血清学诊断、螺旋体的直接检测和螺旋体致死的评估带来更准确的测试。此外，对螺旋体毒力和与严重疾病相关的宿主因素的更多了解可能会为那些将从更密集的治疗中受益的患者开发实验室标记物。

DESCRIPTION (provided by applicant): The goal of this grant proposal is to improve diagnostic testing for Lyme disease and to identify spirochetal and host factors that lead to more severe disease. This goal will be carried out by the analysis of samples from large retrospective and prospective series of well-characterized patients with Lyme disease. For this project, a leading candidate second-generation serologic test, an IgM OspC (C10)-peptide ELISA and an IgG VIsE (IR6)-peptide ELISA, will be assessed prospectively' and compared with the results obtained by whole-cell sonicate ELIoA and Western blot in patients with early or late Lyme disease and in control subjects. Antibody responses to novel glycolipid antigens of B. burgdorferi will be explored to learn whether serial determinations of these responses after antibiotic treatment may serve as a potential surrogate marker for spirochetal killing. The value of quantitative PCR as a diagnostic test will be determined for patients with Lyme disease as compared with standard PCR and culture. The spirochetal burden in skin biopsy samples of erythema migrans (EM) skin lesions and spirochetal virulence factors in isolates from these lesions will be delineated, and the results will be correlated with clinical markers of spirochetal dissemination and severity of infection. Finally, cytokine and chemokine profiles in EM lesions from these patients will be determined and correlated with clinical markers of spirochetal dissemination and severity of infection and with blood test results of cellular and humoral immune function. These studies are likely to lead to more accurate tests for the serodiagnosis of Lyme disease, for direct detection of the spirochete, and for the assessment of spirochetal killing. In addition, greater knowledge of spirochetal virulence and host factors associated with severe disease may allow the development of laboratory markers for patients who would benefit from more intensive treatment.