CLINICAL STUDIES OF ABNORMAL HOST DEFENSE

本项目的目的是研究宿主异常的患者 防御 在1997财政年度，我们继续进行长期的自然历史研究 以及吞噬细胞功能异常患者的发病机制。 这些患者包括儿童慢性肉芽肿性疾病， 高免疫球蛋白E-复发性感染综合征（约伯氏），白细胞 粘连缺陷和其他复发性感染的患者， 不属于特定的疾病类别。 今年我们 继续进行干扰素的IV期临床试验， 对儿童生长发育的影响 肉芽肿性疾病的儿童，并没有注意到任何不利的 反应. 我们继续我们的研究，对一个15岁的女孩与复发性生活 威胁细菌感染谁是难治性的影响， 内毒素脂多糖（LPS）在体内和体外。 我们的研究 在该例对LPS表现出异常发热反应的患者中， TNF-α、IL-6、IL-8、乳铁蛋白和G-CSF应答缺陷 已于今年完成并出版。 我们现在专注于 注意内毒素低反应性的分子基础， 这个病人。 初步数据显示，缺陷涉及NF KB 系统 虽然确切的缺陷尚未确定， 数据表明参与蛋白质合成的激酶系统 磷酸化

The purpose of this project is to study patients with abnormal host defense. In FY'97 we continued our long term studies on natural history and disease pathogenesis on patients with abnormal phagocyte function. These included patients with chronic granulomatous disease of childhood, hyperimunoglobulin E-recurrent infection syndrome (Job's), leukocyte adhesion deficiency and other patients with recurrent infections who do not fall into a specifically defined disease category. This year we continued the phase IV clinical trial on the effect of interferon- gamma on the growth and development of children with chronic granulomatous disease of childhood and failed to note any adverse reactions. We have continued our studies on a 15 yo girl with recurrent life threatening bacterial infections who is refractory to the effects of endotoxin lipopolysaccharide (LPS) in vivo and in vitro. Our studies in this patient demonstrating abnormal febrile response to LPS and defective responses for TNF-alpha, IL-6, IL-8, lactoferrin and G-CSF were completed and published this year. We are now focusing our attention to the molecular basis for endotoxin hyporesponsiveness in this patient. Preliminary data indicates the defect involves the NFKB system. Although the precise defect has not yet been identified the data suggest involvement of a kinase system involved in protein phosphorylation.