Effect Of Cytokines In Host Defense And Inflammation

1)水疱方案被用于评估几个罕见免疫缺陷患者群体的体内炎症，包括STAT 3缺陷、CGD等。 我们的一些STAT 3缺陷研究的结果已提交出版。 使用正常受试者，我们正在与Doug Kuhns（SAIC）合作，以检查人类炎性白细胞作为T细胞功能的髓系抑制细胞的能力。 2)在2012财年期间，我们继续招募患者参加NIH方案#10-I-0123慢性肉芽肿病特定基因突变受试者对IFN-γ的生化反应评估。 这项研究将测试CGD患者的亚群，在潜在的突变和/或残留的NADPH氧化酶活性不同，是否更有可能从IFN-γ治疗中获益。干扰素-γ已在临床上用于CGD患者以降低感染率。然而，这种昂贵药物的作用机制和CGD患者临床反应的广泛差异都不清楚。我们的假设是，只有某些CGD患者亚组，特别是那些具有较高可检测水平的ROS的患者可能对干扰素治疗有反应并从中受益。本研究的完成可能导致显著的成本节约和与干扰素治疗相关的发病率降低。

1) The blister protocol is being used to evaluate inflammation in vivo in several populations of patients with rare immunodeficiencies including STAT3 deficiency, CGD, and others. Results from some of our studies of STAT3 deficiency have been submitted for publication. Using normal subjects, we are collaborating with Doug Kuhns (SAIC), to examine the ability of human inflammatory leukocytes to act as myeloid suppressor cells of T-cell function. 2) During FY12, we have continued to enroll patients in NIH Protocol #10-I-0123 Assessment of the Biochemical Response to IFN-gamma in Subjects with Specific Gene Mutations in Chronic Granulomatous Disease. This study will test whether subpopulations of CGD patients, differing in underlying mutation and/or residual NADPH oxidase activity, are more likely to benefit from IFN-gamma treatment. Interferon-gamma has been used clinically in CGD patients to reduce the rates of infection. However, neither the mechanism of this costly drugs actions nor the wide variation in clinical response among CGD patients is known. Our hypothesis is that only certain subgroups of CGD patients, specifically those with higher detectable levels of ROS may be responsive to and benefit from Interferon treatment. Completion of this study may result in significant cost savings and a reduction in morbidity associated with interferon treatment.