ASPERGILLUS ALLERGENS AND ALLERGIC ASPERGILLOSIS

曲霉过敏原和过敏性曲霉病

• 批准号: 2462172
• 负责人: VISWANATH P KURUP
• 金额: $ 15.76万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-01-01 至 2000-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2462172
• 关键词: Aspergillus; T lymphocyte; aspergillosis; brain mapping; clinical research; communicable disease diagnosis; cytokine; early diagnosis; epitope mapping; fungal antigens; human subject; immunoglobulin E; microorganism immunology; molecular cloning; pathologic process; respiratory infections

DESCRIPTION (Adapted from the applicant's abstract): The overall objectives of this project are to produce and characterize relevant Aspergillus fumigatus (Af) antigens for early diagnosis of Aspergillus and to understand the immunopathogenesis of allergic aspergillosis. Allergic bronchopulmonary aspergillosis (ABPA) is a destructive lung disease frequently occurring in atopic individuals and in cystic fibrosis patients. The diagnosis of the disease is based mostly on immunological criteria, yet our understanding of the immunodiagnosis and immunopathogenesis of this disease is unsatisfactory. Furthermore, due to the lack of reliable reagents and inconsistent reproducibility of assays, the interpretation of the test results are frequently difficulty and less contributory and has been cited as a major reason why more patients are not diagnosed during the early onset of the disease. Four pure antigens from Af obtained through molecular cloning have been identified and all of them demonstrated significant IgE antibody binding and T-cell proliferation activities in ABPA. Both in vitro and in vivo tests will be used to demonstrate Af specific IgE antibodies in the sera of patients using the four recombinant Af antigens. The epitopes binding to IgE will be identified and compared with other known allergens and unique ones will be cloned and expressed. These cloned epitopes bearing polypeptides will be evaluated for their specificity and relevancy in the diagnosis of ABPA. T-cells from ABPA patients will be cloned for understanding the mechanism of the disease by studying the Th1 and Th2 cytokine profile. T-cell lines generated against Asp f2 will be stimulated with synthetic peptides from the sequence of Asp f2, a recombinant protein with reactivity with ABPA< and T-cell epitopes will be identified. The cytokines produced by these clones in response to synthetic T-cell epitopes will be assessed to understand the pathogenesis of the disease. The cytokine profile will add to our knowledge on the pathophysiological events associated with disease. The results of these studies will provide the much needed understanding of the immune mechanism active in ABPA, which in future can be used to control or manage the disease effectively.

描述（改编自申请人的摘要）：总体目标 本项目的主要目的是生产和鉴定相关的曲霉菌 烟曲霉（Af）抗原用于曲霉菌的早期诊断， 过敏性曲霉病的免疫发病机制。 过敏性支气管肺 曲霉病（ABPA）是一种破坏性的肺部疾病， 特应性个体和囊性纤维化患者。 的诊断 疾病主要基于免疫学标准，但我们对 该疾病的免疫诊断和免疫发病机制， 不满意。 此外，由于缺乏可靠的试剂， 试验重现性不一致，试验解释 结果往往是困难的，贡献较小，并已被引用 这是为什么更多的患者在早期发病时没有被诊断出的主要原因 的疾病。 通过分子生物学方法获得了4种Af纯抗原 克隆已被确定，所有这些都表现出显着的IgE ABPA中的抗体结合和T细胞增殖活性。 在体外 体内试验将用于证明Af特异性IgE抗体， 使用四种重组Af抗原的患者血清。 的表位 将鉴定与IgE的结合，并与其他已知过敏原进行比较 独特的基因将被克隆和表达。 这些克隆的表位 将评价多肽在本发明中的特异性和相关性。 ABPA的诊断 ABPA患者的T细胞将被克隆用于 通过对Th1和Th2细胞的研究，了解疾病的发病机制 细胞因子谱。 将刺激针对Asp f2生成的T细胞系 用来自重组蛋白Aspf2序列的合成肽， 将鉴定与ABPA和T细胞表位具有反应性的表位。 的 这些克隆响应合成T细胞表位产生的细胞因子 将进行评估，以了解疾病的发病机制。 的 细胞因子谱将增加我们对病理生理学事件的认识 与疾病有关。 这些研究的结果将提供许多 需要了解ABPA的免疫机制，这在未来 可用于有效控制或管理疾病。