International Research in Thailand

泰国的国际研究

• 批准号: 10928529
• 负责人: Steven Holland
• 金额: $ 28.59万
• 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/10928529
• 关键词: Acquired Immunodeficiency Syndrome; Adult; Antibodies; Asia; Autoantibodies; Biological Assay; Blood Banks; Chickenpox; Chronic Disease; Country; Cryptococcal Meningitis; Cryptococcosis; Cryptococcus gattii; Data; Defect; Diagnostic; Disease; East Asian; Enrollment; Epitopes; Far East; Granulocyte-Macrophage Colony-Stimulating Factor; HIV; Herpes zoster disease; Histoplasmosis; Human; Immune System Diseases; Immunologic Deficiency Syndromes; Immunologics; Infection; Interferon Type II; International; Natural History; Nocardia Infections; Opportunistic Infections; Patients; Pneumocystis; Proteome; Pulmonary Tuberculosis; Reporting; Research; Salmonella infections; Sampling; Site; Syndrome; Taiwan; Thailand; Thymoma; Tuberculosis; United States; cohort; cytokine; design; disease natural history; interleukin-23; non-tuberculosis mycobacteria; non-tuberculous mycobacterial infection; rituximab; screening; Acquired Immunodeficiency Syndrome; Adult; Antibodies; Asia; Autoantibodies; Biological Assay; Blood Banks; Chickenpox; Chronic Disease; Country; Cryptococcal Meningitis; Cryptococcosis; Cryptococcus gattii; Data; Defect; Diagnostic; Disease; East Asian; Enrollment; Epitopes; Far East; Granulocyte-Macrophage Colony-Stimulating Factor; HIV; Herpes zoster disease; Histoplasmosis; Human; Immune System Diseases; Immunologic Deficiency Syndromes; Immunologics; Infection; Interferon Type II; International; Natural History; Nocardia Infections; Opportunistic Infections; Patients; Pneumocystis; Proteome; Pulmonary Tuberculosis; Reporting; Research; Salmonella infections; Sampling; Site; Syndrome; Taiwan; Thailand; Thymoma; Tuberculosis; United States; cohort; cytokine; design; disease natural history; interleukin-23; non-tuberculosis mycobacteria; non-tuberculous mycobacterial infection; rituximab; screening

We enrolled 212 patients into five groups: including those with disseminated nontuberculous mycobacterial disease, severe opportunistic infections, pulmonary tuberculosis, disseminated tuberculosis, and normal blood bank controls. We identified anti-interferon gamma autoantibodies 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, one patient with cryptococcal meningitis had anti-GM-CSF autoantibodies. 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 allows us to identify, follow, and titer anti-interferon gamma activity. The recognition of anti-interferon gamma autoantibodies as the cause of severe opportunistic infections has led to the use of rituximab for control of their antibodies and therefore their infections. These conditions overlap considerably with advanced AIDS, except for the absence of pneumocystis. We are now engaged in characterizing the epitope or epitopes that are being recognized by these autoantibodies. We have also identified autoantibodies to GM-CSF in Cryptococcus gattii infection and extra pulmonary Nocardia infection. Further we have identified anti-IL-23 autoantibodies in other infection syndromes, including thymoma, and this is the target for further study.

我们将212名患者纳入了五组：包括传播的非结核分枝杆菌疾病，严重的机会性感染，肺结核，传播结核病和正常血液库控制的患者。我们确定了大约90％患有机会性的机会感染的抗Interferron伽马自身抗体。所有这些患者均未感染HIV，没有其他公认的免疫功能障碍原因。有趣的是，一名隐球菌脑膜炎患者患有抗GM-CSF自身抗体。因此，我们已经在泰国和台湾的大量患者中表现出严重的机会性感染，包括非结核分枝杆菌，它们会自身抗体对干扰素伽玛的抗病性造成缺陷，并重现严重免疫缺陷的状态。 由于该项目并将这些诊断机会扩展到该领域，我们为抗Interferferon伽马自身抗体开发了一个简单的筛选测定法，使我们能够识别，遵循和介绍抗Inti-Interferon Gamma活性。 抗互化伽马自身抗体作为严重机会感染的原因，导致使用利妥昔单抗控制其抗体及其感染。这些条件与晚期艾滋病的重叠相当大，除了缺乏肺囊肿。 现在，我们正在介绍这些自身抗体所识别的表位或表位。我们还确定了在加氏菌感染和肺部肺炎感染中的GM-CSF的自身抗体。此外，我们已经确定了包括胸腺瘤在内的其他感染综合征中的抗IL-23自身抗体，这是进一步研究的靶标。