'Lyme disease: A possible test for cure

描述（由申请人提供）：这将是非常有用的 莱姆病（LD）治疗的管理，以获得治愈的测试。 这种试验不仅可用于确定急性LD的治疗 是成功的，从而防止过渡到慢性，更 疾病的顽固性形式，而且要区分之间的可能 所谓的治疗后LD综合征的病因。PI和同事 最近开发了一种灵敏和特异的酶联免疫吸附测定法 （ELISA）用于LD的血清学诊断。测试是基于检测 抗体（Ab）的免疫显性不变区（IR）， 脂蛋白VIS E。VIsE是一种分子，它经历抗原变异， 疏螺旋体hurgdorfen（LD的病原体）。一种肽（C6），其代表 VISE的恒定区6（IR 6）作为抗原。据推测 因为螺旋体不能同时在其表面表达 一个以上（或几个）VISE变异（S）在任何时候，VISE脂蛋白必须 被螺旋体迅速翻转和降解，因为新的变体 逐步表达。由于这种假设的内在 不稳定性，VIsE在死亡或垂死的螺旋体上应该是罕见的， 抗体对C6肽的反应应该随着感染的减少而下降。 抗生素治疗后死亡。进一步假设， 治疗后C6 Ab滴度随时间的下降可能有助于 作为治疗莱姆病的试验初步结果表明，C6 ELISA 治愈患者的滴度福尔斯下降大于或等于4倍， 治疗抵抗的患者下降了<4倍。这类似于 VDRL测试用于诊断梅毒治愈。这一广泛的，长期的目标 该项目旨在回顾性和前瞻性地评估 C6 ELISA用作LD治愈的测试。在本提案中，C6测试将是 通过实现三个具体目标进行回顾性评估： 具体目标1：回顾性评估C6 ELISA作为治疗 急性LD患者。来自红斑患者的系列血清样本 移行者（n = 90）和/或培养证实的感染（n = 156）将被 在就诊时以及之后的6个月和12个月采集。样品将 滴定抗C6抗体。 具体目标2：回顾性评估C6 ELISA作为治疗 慢性LD和治疗后LD综合征患者。与SAl相同，但 慢性LD患者（n = 150）和治疗后LD综合征患者（n = 60）。 具体目的3：评估C6 ELISA作为治疗动物模型的试验， LD. LD的治愈将在恒河猴中进行客观评估（通过培养和PCR）， 猴（慢性LD）和小鼠（急性LD）。LD固化与 将评价抗C6 Ab滴度。

DESCRIPTION (provided by applicant): It would be immensely useful for the management of Lyme disease (LD) treatment to have available a test for cure. Such a test could be employed not only to ascertain if treatment of acute LD was successful, thereby preventing the transition to the chronic, more intractable form of the disease, but also to distinguish among the possible etiologies of the so-called post-treatment LD syndrome. The PI and coworkers recently developed a sensitive and specific enzyme-linked immunosorbent assay (ELISA) for the serological diagnosis of LD. The test is based on the detection of antibody (Ab) to an immunodominant, invariable region (lR) of the lipoprotein VIsE. VIsE is the molecule that undergoes antigenic variation in Borrelia hurgdorfen (the etiologic agent of LD). A peptide (C6) representing the invariable region 6 (IR6) of VIsE serves as antigen. It is hypothesized that, because the spirochete should not simultaneously express on its surface more than one (or a few) VIsE variant(s) at any time, the VIsE lipoprotein must be rapidly turned over and degraded by the spirochete as new variants are progressively expressed. As a consequence of this postulated intrinsic instability, VIsE should be scarce on dead or dying spirochetes, and secondary Ab responses to the C6 peptide should decline in unison with the infection's demise, following antibiotic treatment. It is further hypothesized that the decline in titer of the C6 Ab as a function of time after treatment may serve as a test for Lyme disease cure. Preliminary results indicate that the C6 ELISA titer in cured patients falls by a factor greater or equal than 4 whereas for treatment-resistant patients the fall is by a factor <4. This is similar to the VDRL test used to diagnose syphilis cure.The broad, long-term objective of this project is to assess both retrospectively and prospectively the ability of the C6 ELISA to serve as a test for LD cure. In this proposal the C6 test will be assessed retrospectively by achieving three specific aims: Specific Aim 1: To assess retrospectively the C6 ELISA as a test for cure in patients with acute LD. Serial serum samples from patients with either erythema migrans ( n = 90) and/or culture-confirmed infection ( n = 156) will have been collected at presentation and at 6 and 12 months thereafter. The samples will be titrated for anti-C6 Ab. Specific Aim 2: To assess retrospectively the C6 ELISA as a test for cure in patients with chronic LD and post-treatment LD syndrome. Same as for SAl, but with patients with chronic LD (n = 150) and post-treatment LD syndrome (n = 60). Specific Aim 3: To assess the C6 ELISA as a test for cure in animal models of LD. Cure of LD will be assessed objectively (by culture and PCR) both in rhesus monkeys (chronic LD) and in mice (acute LD). Correlation between LD cure and anti-C6 Ab titers will be evaluated.