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，我们已经开始、入组并关闭了新入组的研究，因为我们在6个月内达到了总入组目标。我们将212名患者分为五组，包括严重机会性感染患者、肺结核患者、播散性结核患者和正常人。我们对这些患者的血浆进行了深入分析，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，在约90%的严重机会性感染患者中发现。所有这些患者均未感染HIV，并且没有其他公认的免疫功能障碍原因。有趣的是，肺结核和播散性结核患者的抗干扰素γ自身抗体水平并不显著。这些结果具有高度统计学意义。重要的是，机会性感染患者的整个缺陷似乎都在血浆成分中，因为当这些患者的细胞被清洗干净自己的血浆时，它们的功能正常。此外，在正常细胞中加入抑制性血浆完全重现了体外缺陷。因此，我们在泰国和中国台湾的一个大型队列中发现，包括非结核分枝杆菌在内的严重机会性感染患者，干扰素γ的自身抗体导致了这种缺陷，并重现了严重的免疫缺陷状态。 作为该项目的结果，为了将这些诊断机会扩展到该领域，我们已经开发了一种简单的抗干扰素γ自身抗体筛选试验，使我们能够识别，跟踪和滴定活性。