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名患者分为五组：包括播散性非结核分枝杆菌疾病组、严重机会性感染组、肺结核组、播散性肺结核组和正常血库对照组。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，一名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。 作为该项目的结果，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、跟踪和滴定抗干扰素伽马活性。 认识到抗干扰素-伽马自身抗体是严重机会性感染的原因，因此使用利妥昔单抗来控制其抗体，从而控制其感染。除了没有肺孢子虫外，这些情况与晚期艾滋病有相当大的重叠。 我们现在正致力于鉴定这些自身抗体识别的一个或多个表位。我们还在隐球菌感染和肺外诺卡菌感染中发现了抗GM-CSF的自身抗体。此外，我们已经在包括胸腺瘤在内的其他感染综合征中发现了抗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