Immediate Hypersensitivity Responses--control In Parasit

另一种理解嗜酸性粒细胞激活和调节的主要方法是遗传学方法，我们已经确定了一个家族性嗜酸性粒细胞过多的大亲属。这种综合征是常染色体显性的，并允许相关基因与靠近标记D5S1505的5号染色体的物理连锁。该区域有许多基因，包括白介素5的基因，但随后对IL-5、IL-3和GM-CSF基因及其促进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，对这种疾病采取了一种综合的方法。从他们的细胞和嗜酸性粒细胞收集的数据表明，他们的嗜酸性粒细胞没有主要的活化表型（基于细胞表面标记表达，电子显微镜，嗜酸性粒细胞存活测定），微阵列分析表明了几个可能的候选基因。其他嗜酸性细胞增多症已被广泛研究，我们已经发现了区分嗜酸性细胞增多症的骨髓增生性和淋巴增生性的新标记物。有了这一区别，我们已经制定了新的治疗方法来治疗每一种形式。利用流行病学工具，结合变态反应性疾病的生理测量和免疫学评估，研究了寄生虫感染与变态反应性疾病之间的相互作用。我们已经证明，慢性蠕虫感染可以预防过敏性疾病。

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.