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

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例患者分为五组：包括播散性非结核分枝杆菌病、严重机会性感染、肺结核、播散性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HIV，并且没有其他公认的免疫功能障碍原因。有趣的是，1例隐球菌性脑膜炎患者有抗GM-CSF自身抗体。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，跟踪和滴定抗干扰素γ活性。 认识到抗干扰素γ自身抗体是严重机会性感染的原因，导致使用利妥昔单抗控制其抗体，从而控制其感染。这些情况与晚期艾滋病相当重叠，除了没有肺孢子虫。 我们现在正在研究这些自身抗体识别的表位。我们还确定了自身抗体GM-CSF隐球菌感染和肺外诺卡氏菌感染。此外，我们还在其他感染综合征（包括胸腺瘤）中发现了抗IL-23自身抗体，这是进一步研究的目标。

项目成果

Adult-onset immunodeficiency in Thailand and Taiwan.

• DOI: 10.1056/nejmoa1111160
• 发表时间: 2012-08-23
• 期刊: The New England journal of medicine
• 作者: Browne SK;Burbelo PD;Chetchotisakd P;Suputtamongkol Y;Kiertiburanakul S;Shaw PA;Kirk JL;Jutivorakool K;Zaman R;Ding L;Hsu AP;Patel SY;Olivier KN;Lulitanond V;Mootsikapun P;Anunnatsiri S;Angkasekwinai N;Sathapatayavongs B;Hsueh PR;Shieh CC;Brown MR;Thongnoppakhun W;Claypool R;Sampaio EP;Thepthai C;Waywa D;Dacombe C;Reizes Y;Zelazny AM;Saleeb P;Rosen LB;Mo A;Iadarola M;Holland SM
• 通讯作者: Holland SM