International Research in Thailand

泰国的国际研究

• 批准号: 10274158
• 负责人: Steven Holland
• 金额: $ 21.55万
• 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/10274158
• 关键词: Acquired Immunodeficiency Syndrome; Adult; Antibodies; Asia; Asians; Autoantibodies; Biological Assay; Blood Banks; Chickenpox; Chronic Disease; Country; Cryptococcal Meningitis; Cryptococcosis; Cryptococcus gattii; Data; Defect; Diagnostic; Disease; Enrollment; Epitopes; Far East; Granulocyte-Macrophage Colony-Stimulating Factor; HIV; Herpes zoster disease; Histoplasmosis; Immune System Diseases; Immunologic Deficiency Syndromes; Immunologics; Infection; Interferon Type II; International; Lung; Mycobacterium Infections; Natural History; Nocardia Infections; Opportunistic Infections; Patients; Pneumocystis; Pulmonary Tuberculosis; Reporting; Research; Salmonella infections; Sampling; Site; Taiwan; Thailand; Tuberculosis; United States; cohort; design; disease natural history; non-tuberculosis mycobacteria; 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.

我们将212例患者分为五组：包括弥散性非结核分枝杆菌病、严重机会性感染、肺结核、弥散性肺结核和正常血库对照。我们在大约90%的严重机会性感染患者中发现了抗干扰素γ自身抗体。所有这些患者均未感染艾滋病毒，也没有其他已知的免疫功能障碍原因。有趣的是，一名隐球菌脑膜炎患者有抗gm - csf自身抗体。因此，我们在泰国和台湾的大量患者中发现，严重的机会性感染，包括非结核分枝杆菌，干扰素γ的自身抗体是导致缺陷和再现严重免疫缺陷状态的原因。