Immediate Hypersensitivity Responses--control In Parasit

立即超敏反应——寄生虫的控制

• 批准号: 6669723
• 负责人: THOMAS B NUTMAN
• 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/6669723
• 关键词: Filarioidae; anthelmintics; autosomal dominant trait; cell migration; chemokine; clinical trials; cytokine; enzyme linked immunosorbent assay; eosinophil; eosinophilia; flow cytometry; helminthiasis; helminthic antigen; host organism interaction; human subject; human therapy evaluation; immediate hypersensitivity; immunoglobulin E; immunoglobulin G; immunoregulation; inflammation; nucleic acid sequence; parasitic disease chemotherapy; patient oriented research; polymerase chain reaction; tissue /cell culture

One other major approach taken to understand eosinophil activation and regulation is a genetic approach in which we have identified a large kindred with familial hypereosinophilia. This syndrome is autosomal dominant and has allowed physical linkage of the responsible gene to chromosome 5 near to marker D5S1505. There are a number of genes in the area, including that for interleukin 5, but subsequent complete sequencing of the IL-5, IL-3 and GM-CSF gene and their promotes has not identified the candidate gene or mutation. Over the past several years an integrated approach to this disorder has been taken by studying close to 50 members of the kindred. Data collected on their cells and eosinophils have suggested that their eosinophils are without major activation phenotypes (based on cell surface marker expression, electron microscopy, eosinophil survival assays) and microarray analysis has indicated several possible candidate genes. Other hypereosinophilic conditions have been studied extensively, and we have identified new markers that distinguish between a myeloproliferative and a lymphoproliferative form of the Hyperosinophilic Syndrome. Having made this distinction, we have instituted new therapies for the treatment of each of these forms. The interaction between helminth infeciton and allergic disease has been studied using epidemiological tools coupled with physiological measurements of allergic disease and immunological assessments. We have demonstrated that chronic helminth infection protects against allergic diseases.

另一个主要的方法来了解嗜酸性粒细胞的激活和调节是一个遗传的方法，我们已经确定了一个大的家族性嗜酸性粒细胞增多症的亲属。这种综合征是常染色体显性遗传，并允许物理连锁的责任基因5号染色体附近的标记D5 S1505。该区域有许多基因，包括白细胞介素5，但随后对IL-5，IL-3和GM-CSF基因及其启动子的完整测序尚未确定候选基因或突变。在过去的几年里，通过研究近50名亲属，对这种疾病采取了综合方法。收集到的关于他们的细胞和嗜酸性粒细胞的数据表明，他们的嗜酸性粒细胞没有主要的活化表型（基于细胞表面标志物表达，电子显微镜，嗜酸性粒细胞存活测定）和微阵列分析表明了几个可能的候选基因。其他嗜酸性粒细胞增多症已被广泛研究，我们已经确定了新的标志物，区分骨髓增生性和淋巴增生性形式的嗜酸性粒细胞增多综合征。有了这种区别，我们已经制定了新的疗法来治疗每一种形式。蠕虫感染和过敏性疾病之间的相互作用已经研究了流行病学的工具，加上过敏性疾病的生理测量和免疫学评估。我们已经证明，慢性蠕虫感染可以预防过敏性疾病。