Assessment Of Patients With Lyme Infection

莱姆病是由伯氏疏螺旋体感染引起的一种多系统疾病，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，伯氏杆菌感染主要导致皮肤、神经系统、心脏和关节的感染。莱姆病通常可以用抗生素治疗成功，早期疾病的患者效果最好。不幸的是，一些患者可能对治疗没有完全的反应。持续的疾病体征和症状背后的机制(S)，尽管目前被认为是足够的抗生素治疗，是当今关于莱姆病最有争议的问题之一。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。这两项协议都是自然历史研究，并作为多条调查路线的基础。一种方案针对PTLDS患者和对照组，包括莱姆关节炎患者、莱姆病恢复者、血清阳性但无症状的人、接种OspA疫苗的人、以及健康志愿者和多发性硬化症患者。另一种方案允许对典型莱姆病患者进行研究。关于实验室诊断学，我们一直专注于开发更好的诊断和感染持久性测试。我们与杜兰大学医学中心的Mario Philipp博士和他的团队合作开发了C6多肽酶联免疫吸附试验。这项检测操作简单，具有高度的敏感性和特异性。这种检测的一个重要优点是，它可以用来诊断接种了莱姆病疫苗的患者的莱姆病，而且可以在欧洲使用，在欧洲，莱姆病可能是由加里尼氏杆菌和阿夫泽利杆菌引起的。除了使用C6抗体反应诊断莱姆病外，我们目前正在评估这种反应作为感染清除的可能标记物。与NINDS神经免疫学分会的罗兰·马丁博士合作，我们正在研究伯氏疏螺旋体特异性T细胞克隆的特异性和功能，使用一种新的方法来解密T细胞克隆的抗原特异性。这种方法使用位置扫描、合成组合多肽库和生物计分矩阵，是研究自身免疫机制在莱姆病相关慢性症状发生中的作用以及研究其他感染性和免疫性疾病的有力新工具。在这些研究的后续行动中，我们开发了一种高度特异和敏感的技术来追踪单个T细胞克隆。T细胞克隆型追踪能够进一步阐明自身反应性或病原体特异性T细胞的扩张动力学，这些T细胞介导病理或保护性免疫反应。我们研究了PTLDS患者队列中磁共振(MR)异常的模式。除了T2加权快速自旋回波(FSE)成像外，我们还使用了灵敏的液体衰减反转恢复(FLAIR)序列来增加脑白质病变的潜在良好率。我们还对PTLDS患者的一组患者进行了全脑磁化转移率(MTR)直方图分析，以检测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患者有白质高信号，倾向于发生在皮质下小动脉分水岭区域，且不具特异性。磁化转移率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，以评估神经莱姆病的现有知识。参与者包括来自传染病、神经学、风湿学、基础免疫学和自身免疫病领域的研究人员，主要但不完全专注于莱姆病。这次研讨会的主要目的是评估美国神经疏螺螺旋体病的诊断、治疗和随访的现状，并通过将该领域的科学家聚集在一个支持前沿研究的展示和讨论的环境中来促进研究。

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.