IMMUNOPATHOGENESIS OF LYMPHATIC FILARIASIS

目前围绕丝虫性炎症的免疫学范式有 几乎完全从对外周免疫反应的研究中进化而来。 在人类中，对疾病活动实际部位的组织进行检查， 例如我们现在证明对丝虫病的研究是可行的，提供了 一次不同寻常的机会来研究免疫的致病机制 对人类寄生虫病原体的反应。因为没有足够的 班氏丝虫病动物模型、活检组织和外周血 从巴西班克罗夫蒂疫区的感染者中分离出来的 同时进行了研究。患者最初将被分成3类 根据临床和当前感染情况分组，以便开展 以下3个具体实验目的：1)测定T细胞受体 (TCR)通过比较疾病部位的TCR VB曲目 同一人的感染组织和血液中；2)确定 通过比较细胞因子水平与局部疾病相关的细胞因子 与局部疾病相关的通过比较 不同临床组的活检；以及3)检查 研究对象体内的总蠕虫负担，清除剂量为 大杀丝剂。根据我们公布的初步数据，我们 相信所有感染白纹伊蚊的患者都有疾病 是否有任何明显的临床表现。因此，当前的 丝虫病患者的极地分类 微丝虫病的状况可能不适合于了解当地 组织中的免疫病理事件。我们希望，由于拟议的 工作，以便能够提供相关的框架来进行试运行和 对疾病进行分类以便能够制定有针对性的战略 免疫治疗干预。此外，这些发现可能是宽泛的 适用于其他人体蠕虫的局部组织反应。

The current immunological paradigms surrounding filarial inflammation have evolved almost exclusively from studies of peripheral immune responses. In humans, examination of tissue at the actual site of disease activity, such as we now shown to be feasible for the study of filariasis, provides an unusual opportunity to examine pathogenetic mechanisms of the immune response to a human helminthic pathogen. Because there is no adequate animal model of bancroftian filariasis, biopsy tissue and peripheral blood from infected humans in a W. bancrofti endemic area of Brazil will be simultaneously studied. Patients will be initially classified into 3 groups based on clinical and current infections in order to carry out the following 3 specific experimental aims: 1) Determine the T-cell Receptor (TCR) repertoire at the site of disease by comparing TCR Vb repertoires in infected tissue and in blood of the same individual; 2) Determine the cytokines relevent to local disease by comparing levels of cytokines relevent to local disease by comparing levels of cytokine mRNA from biopsies in the different clinical groups; and 3) Examine the effect of total body worm burden from study subject with a clearing dose of macrofilaricide. Based on our substanstial published preliminary data, we believe that all W. bancrofti infected patients have disease irrespective of the presence of any overt clinical manifestations. Thus, the current polar polar classification of filariasis patients according to clinical or microfilaria status may not be appropriate for understanding local immunopathologic events in tissue. We hope, as a result of the proposed work, to be able to provide a relevent framework for staging and classifying disease in order to be able to develop targetted strategies for immunotherapeutic intervention. Moreover, the findings may be broadly applicable to local tissue reactions in other human helminths.