'Lyme disease: A possible test for cure

描述(由申请人提供)：这将对 莱姆病(LD)治疗的管理有可用的治愈测试。 这样的测试不仅可以用来确定急性LD的治疗 是成功的，从而防止了向慢性、更多 难治性疾病的形式，也要区分可能 所谓的治疗后LD综合征的病因。主办方和同事 最近建立了一种灵敏和特异的酶联免疫吸附试验 (ELISA法)用于LD的血清学诊断。测试的基础是检测 免疫显性不变区(LR)的抗体(Ab) 脂蛋白反之。Vise是一种在体内经历抗原变异的分子 华氏疏螺旋体(LD的病原体)。A肽(C6)代表 以虎钳不变区6(IR6)为抗原。这是假设的 这是因为螺旋体不应该同时在其表面表达 任何时候多个(或几个)虎变异体(S)，虎脂蛋白必须 被螺旋体迅速翻转和降解，因为新的变种 渐进式表达。作为这一假设的内在结果 不稳定，对死亡或濒临死亡的螺旋体应很少使用老虎钳，并继发 AB对C6多肽的反应应该随着感染的下降而下降 抗生素治疗后死亡。进一步的假设是 C6抗体滴度在治疗后随时间的下降可能会 作为莱姆病治愈的试金石。初步结果表明，C6酶联免疫吸附试验 治愈患者的滴度下降了大于或等于4倍，而 耐药患者的下降是一个因素&lt；4。 VDRL试验用于诊断梅毒的治疗。该试验的广泛和长期目标 项目的目的是回顾和前瞻性地评估 C6酶联免疫吸附试验作为LD治愈的检测方法。在这项提案中，C6考试将是 通过实现三个具体目标进行回顾评估： 具体目的1：回顾评价C6-EL ISA作为一种治疗慢性粒细胞白血病的方法 急性LD患者。两种红斑患者的系列血清样本 移民(n=90)和/或经培养确认的感染(n=156)将 在提交时以及之后的6个月和12个月收集。样品将会 被滴定为抗C6抗体。 具体目的2：回顾评价C6-EL ISA作为一种治疗慢性粒细胞白血病的方法 慢性LD患者及治疗后LD综合征患者。和Sal一样，但是 慢性LD患者150例，治疗后LD综合征患者60例。 具体目标3：评价C6-EL ISA在动物模型中的治疗作用 身份证。LD的治愈将在恒河猴身上进行客观的评估(通过培养和PCR) 猴子(慢性LD)和小鼠(急性LD)。LD固化与Ld的相关性研究 将对抗C6抗体效价进行评估。

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.