DIFFERENTIAL SCREENING OF TRYPANOSOMA CRUZI ANTIGENS

克氏锥虫抗原的差异筛选

• 批准号: 2625785
• 负责人: John E Donelson
• 金额: $ 3.91万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2002-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2625785
• 关键词: B lymphocyte; T lymphocyte; Trypanosoma cruzi; autoimmunity; bacterial proteins; cell differentiation; cellular immunity; complementary DNA; cooperative study; enzyme linked immunosorbent assay; gene expression; genetic library; human tissue; humoral immunity; lymphocyte proliferation; microorganism antigen; microorganism genetics; myocardium disorder; recombinant proteins; sign /symptom; trypanosomiasis

Chagas disease is a potentially fatal disease caused by the kinetoplastid protzoan Trypanosoma cruzi. This organism is endemic in most Latin American countries where 16-18 million people are infected, and it constitutes a threat to the blood supply not only in those countries but also in the United States. The majority of chronically infected person are asymptomatic and remain for life in the so-called indeterminate phase of the disease. In 10-30 percent of infected individuals, however, cardiac and gastrointestinal manifestations typical of chronic Chagas disease occur. The study of T. cruzi antigens proposed in this application has three long-term objectives: (1.) to understand the immune processes involved in pathogenesis, (2.) to improve serological methods for diagnosis and (3.) to identify potential candidates for vaccine development. We propose to evaluate recombinant T. cruzi antigens for the humoral and cellular immune responses they elicit in two groups of chronically infected chagasic patients: asymptomatic persons and patients with chagasic cardiomyopathy. These patients have been studied in the Transplantation Immunology Laboratory of the Sao Paulo University Hospital since 1990. By immunoscreening an amastigote cDNA library with these sera, we plan to identify antigens that are recognized by the immune responses of the two groups of patients. Each recombinant antigen will be tested for its reactivity with sera and peripheral blood monocytes (PMBCs) derived from each patient. We hypothesize that two classes of antigens will be found: (a) potentially protective antigens that stimulate B- and/or T cell responses controlling the parasitic infection, responses expected to be more prevalent in asymptomatic patients, and (b) cross-reactive antigens containing epitopes shared by the parasite and mammalian cells that will be more likely identified using sera from cardiac patients with possible autoimmune reactions. Our studies will verify whether there is a correlation between the antibody and/or cellular response to a number of purified parasite antigens and the course of the T. cruzi infection.

Chagas疾病是由Cruzi的动质质体锥虫引起的潜在致命疾病。 在大多数拉丁美洲国家中，这种生物体被感染了16-1800万，它不仅对这些国家而且在美国也构成了血液供应的威胁。大多数慢性感染者无症状，并且在所谓的不确定阶段的疾病阶段仍然存在生命。 然而，在10-30％的受感染个体中，发生了慢性查加斯病的典型心脏和胃肠道表现。 对本申请中提出的克鲁兹抗原的研究具有三个长期目标：（1.）了解发病机理所涉及的免疫过程，（2。）改善诊断血清学方法，并且（3。）以识别疫苗发育的潜在候选者。我们建议评估两组慢性感染的chagasic患者的体液和细胞免疫反应的重组T. cruzi抗原：无症状的患者和患有chagasic心肌病的患者。 自1990年以来，这些患者就已经在圣保罗大学医院的移植免疫学实验室中进行了研究。通过免疫统计使用这些血清的amastigote cDNA文库，我们计划鉴定通过两组患者的免疫反应所识别的抗原。 每种重组抗原的反应性与从每位患者得出的血清和外周血单核细胞（PMBC）的反应性测试。 我们假设将发现两类抗原：（a）刺激控制寄生虫感染的B-和/或T细胞反应的潜在保护性抗原，预计在无症状的患者中预计会更普遍，并且（b）使用Sera-sera-sera可能会识别的副反应性抗原患者的交叉反应性抗原会更普遍。 我们的研究将验证抗体与/或细胞反应之间与许多纯化的寄生虫抗原的反应与t. cruzi感染的过程之间是否存在相关性。