Assessment Of Patients With Lyme Infection

莱姆病感染患者的评估

• 批准号: 6669570
• 负责人: ADRIANA R MARQUES
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6669570
• 关键词: Borrelia; Lyme disease; adolescence (12-20); antibacterial agents; biomarker; child (0-11); chronic disease /disorder; communicable disease diagnosis; diagnosis design /evaluation; disease /disorder etiology; epidemiology; host organism interaction; human subject; human therapy evaluation; magnetic resonance imaging; microorganism disease chemotherapy; neuropsychological tests; patient oriented research; polymerase chain reaction

Lyme disease is a multisystem illness caused by infection with the spirochete Borrelia burgdorferi and it is the leading vector-borne disease in the United States. Lyme disease is also common in Europe (mainly middle Europe and Scandinavia) and also occurs in Russia, China and Japan. In humans, B. burgdorferi infection causes infection primarily in the skin, nervous system, heart and joints. Lyme disease can usually be treated successfully with antibiotic therapy, with the best results seen in patients with early disease. Unfortunately, some patients may not have a complete response to therapy. The mechanism(s) underlying persistent signs and symptoms of disease, despite the administration of what is currently considered to be adequate antibiotic therapy, is one of the most controversial issues regarding Lyme disease today. This syndrome of nonspecific symptoms has been named post-treatment Lyme disease syndrome (PTLDS). We currently have two clinical protocols studying patients with Lyme disease. Both protocols are natural history studies and serve as the basis for multiple lines of investigation. One protocols addresses patients with PTLDS as well as controls, including patients with Lyme arthritis, individuals who recovered from Lyme disease, individuals found to be seropositive but who are asymptomatic, individuals vaccinated with the OspA vaccine, as well as healthy volunteers and patients with multiple sclerosis. The other protocol allow for the study of patients with classical Lyme disease. Regarding laboratory diagnostics, we have focused in developing better tests for both diagnosis and for persistence of infection. We have collaborated with Dr. Mario Philipp and his group at Tulane University Medical Center, in the development of the C6 peptide ELISA. This test is simple to perform and is highly sensitive and specific. An important advantage of this test is that it can be used to diagnose Lyme disease in patients who have received the Lyme disease vaccine, and it can be used in Europe, where Lyme disease may be caused by B. garinii and B. afzelli. Besides the use of the C6 antibody response for diagnosis of Lyme disease, we are currently evaluating this response as a possible marker for clearance of infection. In collaboration with Dr. Roland Martin (Neuroimmunology Branch, NINDS), we are studying the specificity repertoires and function of Borrelia burgdorferi-specific T cell clones using a novel methodology to decrypt the antigen specificity of T cell clones. This methodology uses positional scanning synthetic combinatorial peptide libraries and biometric score matrices and it is a powerful new tool to investigate what role autoimmune mechanisms play in the development of chronic symptoms associated with Lyme disease as well as to study other infectious and immunologic diseases. In follow up to these studies, we developed a highly specific and sensitive technique to track single T cell clones. T cell clonotype tracking enables to further elucidate the dynamics of expansion of autoreactive or pathogen-specific T cells that mediate pathological or protective immune responses. We have investigated the patterns of magnetic resonance (MR) abnormalities in our cohort of patients with PTLDS. We used the sensitive fluid-attenuated inversion recovery (FLAIR) sequence in addition to T2-weighted fast spin echo (FSE) imaging to increase the potential yield of white-matter lesions. We also employed magnetization transfer ratio (MTR) histogram analysis of the whole brain in a subgroup of patients with PTLDS to test for diffuse structural abnormalities of the brain parenchyma, potentially resulting from demyelination or inflammation. We found that a portion of patients with PTLDS had white-matter hyperintensities, which tend to occur in subcortical arteriolar watershed areas and are not specific. Magnetization transfer ratio analysis did not provide evidence for structural abnormalities of the brain parenchyma in patients with nonfocal disease. Together with NINDS and the ORD, we convened a workshop to evaluate the current knowledge in neurologic Lyme disease. Participants included researchers from the fields of infectious diseases, neurology, rheumatology, basic immunology and autoimmune disease, largely but not exclusively focused on Lyme disease. The main purpose of this workshop was to evaluate the current state of art in diagnosis, treatment and follow up of neuroborreliosis in the US, and to facilitate research by bringing together scientists in the field in an environment supportive for the presentation and discussion of cutting edge research.

莱姆病是一种由伯氏疏螺旋体感染引起的多系统疾病，是美国主要的媒介传播疾病。莱姆病在欧洲（主要是中欧和斯堪的纳维亚半岛）也很常见，在俄罗斯、中国和日本也有发生。在人类中，伯氏疏螺旋体感染主要引起皮肤、神经系统、心脏和关节感染。莱姆病通常可以通过抗生素治疗成功治疗，早期疾病患者的效果最好。不幸的是，一些患者可能对治疗没有完全反应。尽管采用了目前被认为是足够的抗生素治疗，但疾病持续体征和症状背后的机制是当今有关莱姆病最具争议的问题之一。这种非特异性症状的综合征被称为治疗后莱姆病综合征（PTLDS）。我们目前有两个研究莱姆病患者的临床方案。这两个协议都是自然历史研究，并作为多线调查的基础。一项方案针对 PTLDS 患者和对照患者，包括莱姆关节炎患者、莱姆病康复者、血清反应呈阳性但无症状的患者、接种 OspA 疫苗的患者以及健康志愿者和多发性硬化症患者。另一个方案允许对患有经典莱姆病的患者进行研究。关于实验室诊断，我们致力于开发更好的诊断和感染持续性测试。我们与杜兰大学医学中心的 Mario Philipp 博士及其团队合作开发了 C6 肽 ELISA。该测试操作简单，灵敏度高且特异性强。该测试的一个重要优点是，它可以用于诊断已接种莱姆病疫苗的患者的莱姆病，并且可以在欧洲使用，因为那里的莱姆病可能是由 B. garinii 和 B. afzelli 引起的。除了使用 C6 抗体反应来诊断莱姆病外，我们目前正在评估这种反应作为清除感染的可能标志。我们与 Roland Martin 博士（NINDS 神经免疫学分部）合作，正在研究伯氏疏螺旋体特异性 T 细胞克隆的特异性库和功能，使用一种新的方法来解密 T 细胞克隆的抗原特异性。该方法使用位置扫描合成组合肽库和生物特征评分矩阵，是研究自身免疫机制在莱姆病相关慢性症状的发展中所起的作用以及研究其他传染病和免疫性疾病的强大新工具。在这些研究的后续过程中，我们开发了一种高度特异性和灵敏的技术来追踪单个 T 细胞克隆。 T 细胞克隆型追踪能够进一步阐明介导病理性或保护性免疫反应的自身反应性或病原体特异性 T 细胞的扩增动态。我们研究了 PTLDS 患者队列中的磁共振 (MR) 异常模式。除了 T2 加权快速自旋回波 (FSE) 成像之外，我们还使用敏感的流体衰减反转恢复 (FLAIR) 序列来增加白质病变的潜在产量。我们还对 PTLDS 患者亚组的整个大脑进行了磁化传输比 (MTR) 直方图分析，以测试可能由脱髓鞘或炎症引起的脑实质弥漫性结构异常。我们发现部分PTLDS患者存在白质高信号，这种情况往往发生在皮质下小动脉分水岭区域，且不具有特异性。磁化传输比分析没有提供非局灶性疾病患者脑实质结构异常的证据。我们与 NINDS 和 ORD 一起召开了一次研讨会，评估神经莱姆病的当前知识。参与者包括来自传染病、神经病学、风湿病学、基础免疫学和自身免疫性疾病领域的研究人员，主要但不限于莱姆病。本次研讨会的主要目的是评估美国神经疏螺旋体病的诊断、治疗和随访的最新技术水平，并通过将该领域的科学家聚集在一个有利于展示和讨论前沿研究的环境中来促进研究。