International Research in Thailand

泰国的国际研究

• 批准号: 8336280
• 负责人: Steven Holland
• 金额: $ 4.35万
• 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/8336280
• 关键词: Accounting; Acquired Immunodeficiency Syndrome; Anonymous Testing; Asians; Autoantibodies; Biological Assay; CD4 Positive T Lymphocytes; Cell Count; Cell physiology; Cells; Chickenpox; Clinical; Country; Defect; Diagnostic; Disease; Enrollment; Far East; Frequencies; Genus Mycobacterium; HIV; Herpes zoster disease; Histoplasmosis; Immune System Diseases; Immunologic Deficiency Syndromes; In Vitro; Infection; Interferon Type II; International; Mycobacterium Infections; Normal Cell; Opportunistic Infections; Patients; Plasma; Protocols documentation; Pulmonary Tuberculosis; Reporting; Research; Salmonella infections; Sampling; Screening procedure; Taiwan; Thailand; Tuberculosis; United States; cohort; cytokine

This past year we have opened, enrolled, and closed our study to new enrollment because we reached our total enrollment target in 6 months. We enrolled 212 patients into five groups, including those with severe opportunistic infections, patients with pulmonary tuberculosis, patients with disseminated tuberculosis, and normals. We have performed in-depth analysis of the plasma from these patients looking for autoantibodies to 41 different cytokines. The only anticytokine autoantibody that was associated with opportunistic infection was the anti-interferon gamma autoantibody, which was found in approximately 90% of those with severe opportunistic infections. All these patients were HIV uninfected and had no other recognized cause of immune dysfunction. Interestingly, those with pulmonary tuberculosis and those with disseminated tuberculosis did not have significant levels of anti-interferon gamma autoantibodies. These results were highly statistically significant. Importantly, the entire defect in those with opportunistic infections seems to be in the plasma component, since when those patients cells were washed clean of their own plasma, their function as normal. Further, addition of inhibitory plasma to normal cells fully recapitulated the defect in vitro. Therefore, we have shown in a large cohort of patients in Thailand and Taiwan with severe opportunistic infections, including nontuberculous mycobacteria, that autoantibodies to interferon gamma account for the defect and reproduce a state of severe immunodeficiency. As a result of this project and in order to extend these diagnostic opportunities to the field, we have developed a simple screening assay for anti-interferon gamma autoantibodies that will allow us to identify, follow, and titer activity.

在过去的一年里，我们开放、招生和关闭了我们的学习，因为我们在6个月内达到了总招生目标。我们将212名患者分成五组，包括严重机会性感染组、肺结核患者、播散性肺结核患者和正常人。我们对这些患者的血浆进行了深入的分析，以寻找41种不同细胞因子的自身抗体。唯一与机会性感染相关的抗细胞因子自身抗体是抗干扰素-γ自身抗体，在大约90%的严重机会性感染患者中发现这种抗体。所有这些患者都没有感染艾滋病毒，也没有其他公认的免疫功能障碍原因。有趣的是，那些患有肺结核病和播散性肺结核的人没有显著水平的抗干扰素伽马自身抗体。这些结果在统计学上具有非常重要的意义。重要的是，机会性感染患者的全部缺陷似乎存在于血浆成分中，因为当这些患者的细胞被清洗掉自己的血浆时，他们的功能正常。此外，在正常细胞中加入抑制血浆，在体外完全重现了这种缺陷。因此，我们在泰国和台湾的一大批严重机会性感染(包括非结核分支杆菌)患者中表明，干扰素伽马的自身抗体可以解释这种缺陷，并复制一种严重的免疫缺陷状态。 作为这一项目的结果，为了将这些诊断机会扩展到现场，我们开发了一种简单的抗干扰素伽马自身抗体筛选方法，使我们能够识别、跟踪和滴度活动。